2xi2 - Revision history

OCA at 10:15, 27 March 2024

OCA — Wed, 27 Mar 2024 10:15:46 GMT

←Older revision		Revision as of 10:15, 27 March 2024
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/POLG_HCV77 POLG_HCV77] Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (PubMed:18033802). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (PubMed:23799612) (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (PubMed:11086025, PubMed:17881511). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (PubMed:14602201). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (PubMed:14602201).[UniProtKB:P26662][UniProtKB:P26664][UniProtKB:P29846][UniProtKB:Q99IB8]<ref>PMID:11086025</ref> <ref>PMID:14602201</ref> <ref>PMID:17881511</ref> <ref>PMID:18033802</ref> <ref>PMID:23799612</ref> Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (PubMed:14990718, PubMed:16894197). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (PubMed:16533059, PubMed:29505618, PubMed:24698129). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (PubMed:25122793, PubMed:29695434, PubMed:24838241). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (PubMed:12970454, PubMed:12356718, PubMed:12913001, PubMed:28404852, PubMed:22767607). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (PubMed:22767607, PubMed:12913001). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (PubMed:22855500). Diffusion of the complex E1/E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (PubMed:12970454, PubMed:24038151, PubMed:12913001, PubMed:20375010, PubMed:19182773) (By similarity).[UniProtKB:Q99IB8]<ref>PMID:12356718</ref> <ref>PMID:12913001</ref> <ref>PMID:12970454</ref> <ref>PMID:14990718</ref> <ref>PMID:16533059</ref> <ref>PMID:16894197</ref> <ref>PMID:19182773</ref> <ref>PMID:20375010</ref> <ref>PMID:22767607</ref> <ref>PMID:22855500</ref> <ref>PMID:24038151</ref> <ref>PMID:24698129</ref> <ref>PMID:24838241</ref> <ref>PMID:25122793</ref> <ref>PMID:28404852</ref> <ref>PMID:29505618</ref> <ref>PMID:29695434</ref> Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (PubMed:14990718, PubMed:16894197). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (PubMed:16533059, PubMed:29505618, PubMed:24698129). The interaction between E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (PubMed:25122793, PubMed:29695434). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (PubMed:29695434). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (PubMed:25122793, PubMed:29695434, PubMed:24838241). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (PubMed:12970454, PubMed:12356718, PubMed:12913001, PubMed:28404852, PubMed:22767607). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (PubMed:22767607, PubMed:12913001). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (PubMed:20375010, PubMed:12970454, PubMed:24038151, PubMed:12913001, PubMed:19182773, PubMed:22855500) (By similarity). Diffusion of the complex E1/E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (PubMed:20375010, PubMed:12970454, PubMed:24038151, PubMed:12913001, PubMed:19182773) (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on DCs, and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (PubMed:15371595). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (PubMed:15371595). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (PubMed:30341327).[UniProtKB:P26664][UniProtKB:Q99IB8]<ref>PMID:12356718</ref> <ref>PMID:12913001</ref> <ref>PMID:12970454</ref> <ref>PMID:14990718</ref> <ref>PMID:15371595</ref> <ref>PMID:16533059</ref> <ref>PMID:16894197</ref> <ref>PMID:19182773</ref> <ref>PMID:20375010</ref> <ref>PMID:22767607</ref> <ref>PMID:22855500</ref> <ref>PMID:24038151</ref> <ref>PMID:24698129</ref> <ref>PMID:24838241</ref> <ref>PMID:25122793</ref> <ref>PMID:28404852</ref> <ref>PMID:29505618</ref> <ref>PMID:29695434</ref> <ref>PMID:30341327</ref> Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (PubMed:12719519, PubMed:20824094, PubMed:27320856). Participates in virus envelopment by coordinating the encounter between NS5A and NS2-based assembly sites loaded with E1/E2 heterodimer, which subsequently leads to nucleocapsid envelopment (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (Probable) (PubMed:20824094). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). The release of Ca(2+) may also activate the inflamasome leading to chronic inflammation (Probable) (PubMed:31801866). Targets also host mitochondria and induces mitochondrial depolarization (PubMed:29039530). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (PubMed:27320856).[UniProtKB:Q99IB8]<ref>PMID:12719519</ref> <ref>PMID:20824094</ref> <ref>PMID:27320856</ref> <ref>PMID:29039530</ref> <ref>PMID:31801866</ref> <ref>PMID:14741348</ref> <ref>PMID:24006444</ref> Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (PubMed:8248148). The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (By similarity). Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (PubMed:21147927).[UniProtKB:P26663]<ref>PMID:21147927</ref> <ref>PMID:8248148</ref> Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (PubMed:25551442). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (PubMed:8189513, PubMed:8035505, PubMed:8386278). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (PubMed:30341327). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (Probable). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (PubMed:21940894). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (PubMed:16301520, PubMed:16177806). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (PubMed:15710891).[UniProtKB:Q9WMX2]<ref>PMID:15710891</ref> <ref>PMID:16177806</ref> <ref>PMID:16301520</ref> <ref>PMID:21940894</ref> <ref>PMID:25551442</ref> <ref>PMID:30341327</ref> <ref>PMID:8035505</ref> <ref>PMID:8189513</ref> <ref>PMID:8386278</ref> <ref>PMID:15269774</ref> Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (PubMed:8189513, PubMed:21507982). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (PubMed:30341327).[UniProtKB:Q9WMX2]<ref>PMID:21507982</ref> <ref>PMID:30341327</ref> <ref>PMID:8189513</ref> Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (PubMed:12021330). This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (PubMed:12021330). NS4B self-interaction contributes to its function in membranous web formation (PubMed:16731940). Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (PubMed:29782532). Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (PubMed:23542348).<ref>PMID:12021330</ref> <ref>PMID:16731940</ref> <ref>PMID:23542348</ref> <ref>PMID:29782532</ref> Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (Probable). Zinc is essential for RNA-binding (PubMed:20926572). Participates in the viral particle production as a result of its interaction with the viral mature core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (PubMed:16951545). Prevents BIN1-induced apoptosis (PubMed:16530520). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (PubMed:31801866). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (PubMed:28743875).[UniProtKB:P26662][UniProtKB:P26664][UniProtKB:Q99IB8][UniProtKB:Q9WMX2]<ref>PMID:16530520</ref> <ref>PMID:16951545</ref> <ref>PMID:20926572</ref> <ref>PMID:28743875</ref> <ref>PMID:31801866</ref> <ref>PMID:20926572</ref> RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication.<ref>PMID:20729191</ref>		[https://www.uniprot.org/uniprot/POLG_HCV77 POLG_HCV77] Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (PubMed:18033802). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (PubMed:23799612) (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (PubMed:11086025, PubMed:17881511). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (PubMed:14602201). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (PubMed:14602201).[UniProtKB:P26662][UniProtKB:P26664][UniProtKB:P29846][UniProtKB:Q99IB8]<ref>PMID:11086025</ref> <ref>PMID:14602201</ref> <ref>PMID:17881511</ref> <ref>PMID:18033802</ref> <ref>PMID:23799612</ref> Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (PubMed:14990718, PubMed:16894197). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (PubMed:16533059, PubMed:29505618, PubMed:24698129). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (PubMed:25122793, PubMed:29695434, PubMed:24838241). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (PubMed:12970454, PubMed:12356718, PubMed:12913001, PubMed:28404852, PubMed:22767607). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (PubMed:22767607, PubMed:12913001). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (PubMed:22855500). Diffusion of the complex E1/E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (PubMed:12970454, PubMed:24038151, PubMed:12913001, PubMed:20375010, PubMed:19182773) (By similarity).[UniProtKB:Q99IB8]<ref>PMID:12356718</ref> <ref>PMID:12913001</ref> <ref>PMID:12970454</ref> <ref>PMID:14990718</ref> <ref>PMID:16533059</ref> <ref>PMID:16894197</ref> <ref>PMID:19182773</ref> <ref>PMID:20375010</ref> <ref>PMID:22767607</ref> <ref>PMID:22855500</ref> <ref>PMID:24038151</ref> <ref>PMID:24698129</ref> <ref>PMID:24838241</ref> <ref>PMID:25122793</ref> <ref>PMID:28404852</ref> <ref>PMID:29505618</ref> <ref>PMID:29695434</ref> Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (PubMed:14990718, PubMed:16894197). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (PubMed:16533059, PubMed:29505618, PubMed:24698129). The interaction between E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (PubMed:25122793, PubMed:29695434). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (PubMed:29695434). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (PubMed:25122793, PubMed:29695434, PubMed:24838241). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (PubMed:12970454, PubMed:12356718, PubMed:12913001, PubMed:28404852, PubMed:22767607). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (PubMed:22767607, PubMed:12913001). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (PubMed:20375010, PubMed:12970454, PubMed:24038151, PubMed:12913001, PubMed:19182773, PubMed:22855500) (By similarity). Diffusion of the complex E1/E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (PubMed:20375010, PubMed:12970454, PubMed:24038151, PubMed:12913001, PubMed:19182773) (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on DCs, and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (PubMed:15371595). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (PubMed:15371595). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (PubMed:30341327).[UniProtKB:P26664][UniProtKB:Q99IB8]<ref>PMID:12356718</ref> <ref>PMID:12913001</ref> <ref>PMID:12970454</ref> <ref>PMID:14990718</ref> <ref>PMID:15371595</ref> <ref>PMID:16533059</ref> <ref>PMID:16894197</ref> <ref>PMID:19182773</ref> <ref>PMID:20375010</ref> <ref>PMID:22767607</ref> <ref>PMID:22855500</ref> <ref>PMID:24038151</ref> <ref>PMID:24698129</ref> <ref>PMID:24838241</ref> <ref>PMID:25122793</ref> <ref>PMID:28404852</ref> <ref>PMID:29505618</ref> <ref>PMID:29695434</ref> <ref>PMID:30341327</ref> Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (PubMed:12719519, PubMed:20824094, PubMed:27320856). Participates in virus envelopment by coordinating the encounter between NS5A and NS2-based assembly sites loaded with E1/E2 heterodimer, which subsequently leads to nucleocapsid envelopment (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (Probable) (PubMed:20824094). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). The release of Ca(2+) may also activate the inflamasome leading to chronic inflammation (Probable) (PubMed:31801866). Targets also host mitochondria and induces mitochondrial depolarization (PubMed:29039530). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (PubMed:27320856).[UniProtKB:Q99IB8]<ref>PMID:12719519</ref> <ref>PMID:20824094</ref> <ref>PMID:27320856</ref> <ref>PMID:29039530</ref> <ref>PMID:31801866</ref> <ref>PMID:14741348</ref> <ref>PMID:24006444</ref> Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (PubMed:8248148). The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (By similarity). Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (PubMed:21147927).[UniProtKB:P26663]<ref>PMID:21147927</ref> <ref>PMID:8248148</ref> Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (PubMed:25551442). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (PubMed:8189513, PubMed:8035505, PubMed:8386278). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (PubMed:30341327). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (Probable). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (PubMed:21940894). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (PubMed:16301520, PubMed:16177806). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (PubMed:15710891).[UniProtKB:Q9WMX2]<ref>PMID:15710891</ref> <ref>PMID:16177806</ref> <ref>PMID:16301520</ref> <ref>PMID:21940894</ref> <ref>PMID:25551442</ref> <ref>PMID:30341327</ref> <ref>PMID:8035505</ref> <ref>PMID:8189513</ref> <ref>PMID:8386278</ref> <ref>PMID:15269774</ref> Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (PubMed:8189513, PubMed:21507982). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (PubMed:30341327).[UniProtKB:Q9WMX2]<ref>PMID:21507982</ref> <ref>PMID:30341327</ref> <ref>PMID:8189513</ref> Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (PubMed:12021330). This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (PubMed:12021330). NS4B self-interaction contributes to its function in membranous web formation (PubMed:16731940). Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (PubMed:29782532). Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (PubMed:23542348).<ref>PMID:12021330</ref> <ref>PMID:16731940</ref> <ref>PMID:23542348</ref> <ref>PMID:29782532</ref> Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (Probable). Zinc is essential for RNA-binding (PubMed:20926572). Participates in the viral particle production as a result of its interaction with the viral mature core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (PubMed:16951545). Prevents BIN1-induced apoptosis (PubMed:16530520). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (PubMed:31801866). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (PubMed:28743875).[UniProtKB:P26662][UniProtKB:P26664][UniProtKB:Q99IB8][UniProtKB:Q9WMX2]<ref>PMID:16530520</ref> <ref>PMID:16951545</ref> <ref>PMID:20926572</ref> <ref>PMID:28743875</ref> <ref>PMID:31801866</ref> <ref>PMID:20926572</ref> RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication.<ref>PMID:20729191</ref>
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-	== Publication Abstract from PubMed ==
-	The hepatitis C virus (HCV) NS5b protein is an RNA-dependent RNA polymerase essential for replication of the viral RNA genome. In vitro and presumably in vivo, NS5b initiates RNA synthesis by a de novo mechanism. Different structural elements of NS5b have been reported to participate in RNA synthesis, especially a so-called "beta-flap" and a C-terminal segment (designated "linker") that connects the catalytic core of NS5b to a transmembrane anchor. High concentrations of GTP have also been shown to stimulate de novo RNA synthesis by HCV NS5b. Here we describe a combined structural and functional analysis of genotype 1 HCV-NS5b of strains H77 (subtype 1a), for which no structure has been previously reported, and J4 (subtype 1b). Our results highlight the linker as directly involved in lifting the first boundary to processive RNA synthesis, the formation of the first dinucleotide primer. The transition from this first dinucleotide primer state to processive RNA synthesis requires removal of the linker and of the beta-flap with which it is shown to strongly interact in crystal structures of HCV NS5b. We find that GTP specifically stimulates this transition irrespective of its incorporation in neosynthesized RNA.
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-	Further insights into the roles of GTP and the C terminus of the hepatitis C virus polymerase in the initiation of RNA synthesis.,Harrus D, Ahmed-El-Sayed N, Simister PC, Miller S, Triconnet M, Hagedorn CH, Mahias K, Rey FA, Astier-Gin T, Bressanelli S J Biol Chem. 2010 Oct 22;285(43):32906-18. Epub 2010 Aug 20. PMID:20729191<ref>PMID:20729191</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 2xi2" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 10:32, 20 December 2023

OCA — Wed, 20 Dec 2023 10:32:14 GMT

←Older revision		Revision as of 10:32, 20 December 2023
Line 3:		Line 3:
	<StructureSection load='2xi2' size='340' side='right'caption='[[2xi2]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='2xi2' size='340' side='right'caption='[[2xi2]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2xi2]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/~~9hepc 9hepc~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XI2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2xi2]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_C Hepacivirus C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XI2 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.8Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1onb\|1onb]], [[1r7c\|1r7c]], [[1r7f\|1r7f]], [[1rgq\|1rgq]], [[1cwx\|1cwx]], [[1n1l\|1n1l]], [[1r7d\|1r7d]], [[1a1r\|1a1r]], [[1r7g\|1r7g]], [[1a1v\|1a1v]], [[1hei\|1hei]], [[1r7e\|1r7e]], [[1jr6\|1jr6]], [[2xi3\|2xi3]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr~~ id~~='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[https://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48]~~ </~~span~~></td></tr>	+
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xi2 OCA], [https://pdbe.org/2xi2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xi2 RCSB], [https://www.ebi.ac.uk/pdbsum/2xi2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xi2 ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xi2 OCA], [https://pdbe.org/2xi2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xi2 RCSB], [https://www.ebi.ac.uk/pdbsum/2xi2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xi2 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/POLG_HCVH POLG_HCVH]] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).<ref>PMID:16894197</ref> E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity).<ref>PMID:16894197</ref> P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine (By similarity). Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity.<ref>PMID:16894197</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:16894197</ref> NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand (By similarity). Cleaves and inhibits the host antiviral protein MAVS.<ref>PMID:16894197</ref> NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex. NS4B polymerization or in protein-protein interactions activity may contribute to its function in membranous web formation.<ref>PMID:16894197</ref> NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity).<ref>PMID:16894197</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication.<ref>PMID:16894197</ref>	+	[https://www.uniprot.org/uniprot/POLG_HCV77 POLG_HCV77] Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (PubMed:18033802). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (PubMed:23799612) (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (PubMed:11086025, PubMed:17881511). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (PubMed:14602201). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (PubMed:14602201).[UniProtKB:P26662][UniProtKB:P26664][UniProtKB:P29846][UniProtKB:Q99IB8]<ref>PMID:11086025</ref> <ref>PMID:14602201</ref> <ref>PMID:17881511</ref> <ref>PMID:18033802</ref> <ref>PMID:23799612</ref> Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (PubMed:14990718, PubMed:16894197). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (PubMed:16533059, PubMed:29505618, PubMed:24698129). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (PubMed:25122793, PubMed:29695434, PubMed:24838241). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (PubMed:12970454, PubMed:12356718, PubMed:12913001, PubMed:28404852, PubMed:22767607). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (PubMed:22767607, PubMed:12913001). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (PubMed:22855500). Diffusion of the complex E1/E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (PubMed:12970454, PubMed:24038151, PubMed:12913001, PubMed:20375010, PubMed:19182773) (By similarity).[UniProtKB:Q99IB8]<ref>PMID:12356718</ref> <ref>PMID:12913001</ref> <ref>PMID:12970454</ref> <ref>PMID:14990718</ref> <ref>PMID:16533059</ref> <ref>PMID:16894197</ref> <ref>PMID:19182773</ref> <ref>PMID:20375010</ref> <ref>PMID:22767607</ref> <ref>PMID:22855500</ref> <ref>PMID:24038151</ref> <ref>PMID:24698129</ref> <ref>PMID:24838241</ref> <ref>PMID:25122793</ref> <ref>PMID:28404852</ref> <ref>PMID:29505618</ref> <ref>PMID:29695434</ref> Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (PubMed:14990718, PubMed:16894197). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (PubMed:16533059, PubMed:29505618, PubMed:24698129). The interaction between E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (PubMed:25122793, PubMed:29695434). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (PubMed:29695434). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (PubMed:25122793, PubMed:29695434, PubMed:24838241). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (PubMed:12970454, PubMed:12356718, PubMed:12913001, PubMed:28404852, PubMed:22767607). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (PubMed:22767607, PubMed:12913001). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (PubMed:20375010, PubMed:12970454, PubMed:24038151, PubMed:12913001, PubMed:19182773, PubMed:22855500) (By similarity). Diffusion of the complex E1/E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (PubMed:20375010, PubMed:12970454, PubMed:24038151, PubMed:12913001, PubMed:19182773) (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on DCs, and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (PubMed:15371595). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (PubMed:15371595). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (PubMed:30341327).[UniProtKB:P26664][UniProtKB:Q99IB8]<ref>PMID:12356718</ref> <ref>PMID:12913001</ref> <ref>PMID:12970454</ref> <ref>PMID:14990718</ref> <ref>PMID:15371595</ref> <ref>PMID:16533059</ref> <ref>PMID:16894197</ref> <ref>PMID:19182773</ref> <ref>PMID:20375010</ref> <ref>PMID:22767607</ref> <ref>PMID:22855500</ref> <ref>PMID:24038151</ref> <ref>PMID:24698129</ref> <ref>PMID:24838241</ref> <ref>PMID:25122793</ref> <ref>PMID:28404852</ref> <ref>PMID:29505618</ref> <ref>PMID:29695434</ref> <ref>PMID:30341327</ref> Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (PubMed:12719519, PubMed:20824094, PubMed:27320856). Participates in virus envelopment by coordinating the encounter between NS5A and NS2-based assembly sites loaded with E1/E2 heterodimer, which subsequently leads to nucleocapsid envelopment (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (Probable) (PubMed:20824094). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). The release of Ca(2+) may also activate the inflamasome leading to chronic inflammation (Probable) (PubMed:31801866). Targets also host mitochondria and induces mitochondrial depolarization (PubMed:29039530). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (PubMed:27320856).[UniProtKB:Q99IB8]<ref>PMID:12719519</ref> <ref>PMID:20824094</ref> <ref>PMID:27320856</ref> <ref>PMID:29039530</ref> <ref>PMID:31801866</ref> <ref>PMID:14741348</ref> <ref>PMID:24006444</ref> Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (PubMed:8248148). The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (By similarity). Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (PubMed:21147927).[UniProtKB:P26663]<ref>PMID:21147927</ref> <ref>PMID:8248148</ref> Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (PubMed:25551442). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (PubMed:8189513, PubMed:8035505, PubMed:8386278). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (PubMed:30341327). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (Probable). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (PubMed:21940894). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (PubMed:16301520, PubMed:16177806). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (PubMed:15710891).[UniProtKB:Q9WMX2]<ref>PMID:15710891</ref> <ref>PMID:16177806</ref> <ref>PMID:16301520</ref> <ref>PMID:21940894</ref> <ref>PMID:25551442</ref> <ref>PMID:30341327</ref> <ref>PMID:8035505</ref> <ref>PMID:8189513</ref> <ref>PMID:8386278</ref> <ref>PMID:15269774</ref> Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (PubMed:8189513, PubMed:21507982). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (PubMed:30341327).[UniProtKB:Q9WMX2]<ref>PMID:21507982</ref> <ref>PMID:30341327</ref> <ref>PMID:8189513</ref> Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (PubMed:12021330). This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (PubMed:12021330). NS4B self-interaction contributes to its function in membranous web formation (PubMed:16731940). Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (PubMed:29782532). Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (PubMed:23542348).<ref>PMID:12021330</ref> <ref>PMID:16731940</ref> <ref>PMID:23542348</ref> <ref>PMID:29782532</ref> Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (Probable). Zinc is essential for RNA-binding (PubMed:20926572). Participates in the viral particle production as a result of its interaction with the viral mature core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (PubMed:16951545). Prevents BIN1-induced apoptosis (PubMed:16530520). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (PubMed:31801866). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (PubMed:28743875).[UniProtKB:P26662][UniProtKB:P26664][UniProtKB:Q99IB8][UniProtKB:Q9WMX2]<ref>PMID:16530520</ref> <ref>PMID:16951545</ref> <ref>PMID:20926572</ref> <ref>PMID:28743875</ref> <ref>PMID:31801866</ref> <ref>PMID:20926572</ref> RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication.<ref>PMID:20729191</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Hepacivirus C]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: RNA-directed RNA polymerase]]~~	+	[[Category: Ahmed-El-Sayed N]]
-	[[Category: Ahmed-El-Sayed, N]]	+	[[Category: Astier-Gin T]]
-	[[Category: Astier-Gin, T]]	+	[[Category: Bressanelli S]]
-	[[Category: Bressanelli, S]]	+	[[Category: Hagedorn CH]]
-	[[Category: Hagedorn~~, C H~~]]	+	[[Category: Harrus D]]
-	[[Category: Harrus, D]]	+	[[Category: Mahias K]]
-	[[Category: Mahias, K]]	+	[[Category: Miller S]]
-	[[Category: Miller, S]]	+	[[Category: Rey FA]]
-	[[Category: Rey~~, F A~~]]	+	[[Category: Simister PC]]
-	[[Category: Simister~~, P C~~]]	+	[[Category: Triconnet M]]
-	[[Category: Triconnet, M]]	+
-	~~[[Category: De novo priming]]~~	+
-	~~[[Category: Nonstructural protein]]~~	+
-	~~[[Category: Rdrp]]~~	+
-	~~[[Category: Replication]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 10:53, 13 April 2022

OCA — Wed, 13 Apr 2022 10:53:24 GMT

←Older revision		Revision as of 10:53, 13 April 2022
Line 3:		Line 3:
	<StructureSection load='2xi2' size='340' side='right'caption='[[2xi2]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='2xi2' size='340' side='right'caption='[[2xi2]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2xi2]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=2XI2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2xi2]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XI2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1onb\|1onb]], [[1r7c\|1r7c]], [[1r7f\|1r7f]], [[1rgq\|1rgq]], [[1cwx\|1cwx]], [[1n1l\|1n1l]], [[1r7d\|1r7d]], [[1a1r\|1a1r]], [[1r7g\|1r7g]], [[1a1v\|1a1v]], [[1hei\|1hei]], [[1r7e\|1r7e]], [[1jr6\|1jr6]], [[2xi3\|2xi3]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1onb\|1onb]], [[1r7c\|1r7c]], [[1r7f\|1r7f]], [[1rgq\|1rgq]], [[1cwx\|1cwx]], [[1n1l\|1n1l]], [[1r7d\|1r7d]], [[1a1r\|1a1r]], [[1r7g\|1r7g]], [[1a1v\|1a1v]], [[1hei\|1hei]], [[1r7e\|1r7e]], [[1jr6\|1jr6]], [[2xi3\|2xi3]]</div></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=2xi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xi2 OCA], [~~http~~://pdbe.org/2xi2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2xi2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2xi2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2xi2 ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xi2 OCA], [https://pdbe.org/2xi2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xi2 RCSB], [https://www.ebi.ac.uk/pdbsum/2xi2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xi2 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/POLG_HCVH POLG_HCVH]] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).<ref>PMID:16894197</ref> E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity).<ref>PMID:16894197</ref> P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine (By similarity). Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity.<ref>PMID:16894197</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:16894197</ref> NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand (By similarity). Cleaves and inhibits the host antiviral protein MAVS.<ref>PMID:16894197</ref> NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex. NS4B polymerization or in protein-protein interactions activity may contribute to its function in membranous web formation.<ref>PMID:16894197</ref> NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity).<ref>PMID:16894197</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication.<ref>PMID:16894197</ref>	+	[[https://www.uniprot.org/uniprot/POLG_HCVH POLG_HCVH]] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).<ref>PMID:16894197</ref> E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity).<ref>PMID:16894197</ref> P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine (By similarity). Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity.<ref>PMID:16894197</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:16894197</ref> NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand (By similarity). Cleaves and inhibits the host antiviral protein MAVS.<ref>PMID:16894197</ref> NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex. NS4B polymerization or in protein-protein interactions activity may contribute to its function in membranous web formation.<ref>PMID:16894197</ref> NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity).<ref>PMID:16894197</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication.<ref>PMID:16894197</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 15:15, 8 July 2020

OCA — Wed, 08 Jul 2020 15:15:09 GMT

←Older revision		Revision as of 15:15, 8 July 2020
Line 1:		Line 1:

	==HCV-H77 NS5B Apo Polymerase==		==HCV-H77 NS5B Apo Polymerase==
-	<StructureSection load='2xi2' size='340' side='right' caption='[[2xi2]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='2xi2' size='340' side='right'caption='[[2xi2]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2xi2]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2XI2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2xi2]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2XI2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1onb\|1onb]], [[1r7c\|1r7c]], [[1r7f\|1r7f]], [[1rgq\|1rgq]], [[1cwx\|1cwx]], [[1n1l\|1n1l]], [[1r7d\|1r7d]], [[1a1r\|1a1r]], [[1r7g\|1r7g]], [[1a1v\|1a1v]], [[1hei\|1hei]], [[1r7e\|1r7e]], [[1jr6\|1jr6]], [[2xi3\|2xi3]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1onb\|1onb]], [[1r7c\|1r7c]], [[1r7f\|1r7f]], [[1rgq\|1rgq]], [[1cwx\|1cwx]], [[1n1l\|1n1l]], [[1r7d\|1r7d]], [[1a1r\|1a1r]], [[1r7g\|1r7g]], [[1a1v\|1a1v]], [[1hei\|1hei]], [[1r7e\|1r7e]], [[1jr6\|1jr6]], [[2xi3\|2xi3]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2xi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xi2 OCA], [http://pdbe.org/2xi2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xi2 RCSB], [http://www.ebi.ac.uk/pdbsum/2xi2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xi2 ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2xi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xi2 OCA], [http://pdbe.org/2xi2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xi2 RCSB], [http://www.ebi.ac.uk/pdbsum/2xi2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xi2 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 22:		Line 22:

	==See Also==		==See Also==
-	*[[RNA polymerase\|RNA polymerase]]	+	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
	[[Category: Ahmed-El-Sayed, N]]		[[Category: Ahmed-El-Sayed, N]]

OCA at 09:05, 3 October 2018

OCA — Wed, 03 Oct 2018 09:05:27 GMT

←Older revision		Revision as of 09:05, 3 October 2018
Line 1:		Line 1:

-	==HCV-H77 NS5B ~~APO POLYMERASE~~==	+	==HCV-H77 NS5B Apo Polymerase==
	<StructureSection load='2xi2' size='340' side='right' caption='[[2xi2]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='2xi2' size='340' side='right' caption='[[2xi2]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==

OCA at 11:47, 5 August 2016

OCA — Fri, 05 Aug 2016 11:47:19 GMT

←Older revision		Revision as of 11:47, 5 August 2016
Line 1:		Line 1:
		+
	==HCV-H77 NS5B APO POLYMERASE==		==HCV-H77 NS5B APO POLYMERASE==
	<StructureSection load='2xi2' size='340' side='right' caption='[[2xi2]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='2xi2' size='340' side='right' caption='[[2xi2]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2xi2]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Hepatitis_c_virus Hepatitis c virus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XI2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2xi2]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XI2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1onb\|1onb]], [[1r7c\|1r7c]], [[1r7f\|1r7f]], [[1rgq\|1rgq]], [[1cwx\|1cwx]], [[1n1l\|1n1l]], [[1r7d\|1r7d]], [[1a1r\|1a1r]], [[1r7g\|1r7g]], [[1a1v\|1a1v]], [[1hei\|1hei]], [[1r7e\|1r7e]], [[1jr6\|1jr6]], [[2xi3\|2xi3]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1onb\|1onb]], [[1r7c\|1r7c]], [[1r7f\|1r7f]], [[1rgq\|1rgq]], [[1cwx\|1cwx]], [[1n1l\|1n1l]], [[1r7d\|1r7d]], [[1a1r\|1a1r]], [[1r7g\|1r7g]], [[1a1v\|1a1v]], [[1hei\|1hei]], [[1r7e\|1r7e]], [[1jr6\|1jr6]], [[2xi3\|2xi3]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xi2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xi2 RCSB], [http://www.ebi.ac.uk/pdbsum/2xi2 PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xi2 OCA], [http://pdbe.org/2xi2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xi2 RCSB], [http://www.ebi.ac.uk/pdbsum/2xi2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xi2 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 2xi2" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Hepatitis c virus]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
	[[Category: Ahmed-El-Sayed, N]]		[[Category: Ahmed-El-Sayed, N]]

OCA at 02:10, 25 December 2014

OCA — Thu, 25 Dec 2014 02:10:09 GMT

←Older revision		Revision as of 02:10, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2xi2]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XI2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2xi2]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XI2 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1onb\|1onb]], [[1r7c\|1r7c]], [[1r7f\|1r7f]], [[1rgq\|1rgq]], [[1cwx\|1cwx]], [[1n1l\|1n1l]], [[1r7d\|1r7d]], [[1a1r\|1a1r]], [[1r7g\|1r7g]], [[1a1v\|1a1v]], [[1hei\|1hei]], [[1r7e\|1r7e]], [[1jr6\|1jr6]], [[2xi3\|2xi3]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1onb\|1onb]], [[1r7c\|1r7c]], [[1r7f\|1r7f]], [[1rgq\|1rgq]], [[1cwx\|1cwx]], [[1n1l\|1n1l]], [[1r7d\|1r7d]], [[1a1r\|1a1r]], [[1r7g\|1r7g]], [[1a1v\|1a1v]], [[1hei\|1hei]], [[1r7e\|1r7e]], [[1jr6\|1jr6]], [[2xi3\|2xi3]]</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xi2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xi2 RCSB], [http://www.ebi.ac.uk/pdbsum/2xi2 PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xi2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xi2 RCSB], [http://www.ebi.ac.uk/pdbsum/2xi2 PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/POLG_HCVH POLG_HCVH]] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).<ref>PMID:16894197</ref> E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity).<ref>PMID:16894197</ref> P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine (By similarity). Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity.<ref>PMID:16894197</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:16894197</ref> NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand (By similarity). Cleaves and inhibits the host antiviral protein MAVS.<ref>PMID:16894197</ref> NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex. NS4B polymerization or in protein-protein interactions activity may contribute to its function in membranous web formation.<ref>PMID:16894197</ref> NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity).<ref>PMID:16894197</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication.<ref>PMID:16894197</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 27:
	[[Category: Hepatitis c virus]]		[[Category: Hepatitis c virus]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
-	[[Category: Ahmed-El-Sayed, N.]]	+	[[Category: Ahmed-El-Sayed, N]]
-	[[Category: Astier-Gin, T.]]	+	[[Category: Astier-Gin, T]]
-	[[Category: Bressanelli, S.]]	+	[[Category: Bressanelli, S]]
-	[[Category: Hagedorn, C H.]]	+	[[Category: Hagedorn, C H]]
-	[[Category: Harrus, D.]]	+	[[Category: Harrus, D]]
-	[[Category: Mahias, K.]]	+	[[Category: Mahias, K]]
-	[[Category: Miller, S.]]	+	[[Category: Miller, S]]
-	[[Category: Rey, F A.]]	+	[[Category: Rey, F A]]
-	[[Category: Simister, P C.]]	+	[[Category: Simister, P C]]
-	[[Category: Triconnet, M.]]	+	[[Category: Triconnet, M]]
	[[Category: De novo priming]]		[[Category: De novo priming]]
	[[Category: Nonstructural protein]]		[[Category: Nonstructural protein]]

OCA at 00:53, 2 October 2014

OCA — Thu, 02 Oct 2014 00:53:07 GMT

←Older revision		Revision as of 00:53, 2 October 2014
Line 1:		Line 1:
-	[[~~Image:~~2xi2.~~png~~\|~~left~~\|~~200px~~]]	+	==HCV-H77 NS5B APO POLYMERASE==
		+	<StructureSection load='2xi2' size='340' side='right' caption='[[2xi2]], [[Resolution\|resolution]] 1.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2xi2]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XI2 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1onb\|1onb]], [[1r7c\|1r7c]], [[1r7f\|1r7f]], [[1rgq\|1rgq]], [[1cwx\|1cwx]], [[1n1l\|1n1l]], [[1r7d\|1r7d]], [[1a1r\|1a1r]], [[1r7g\|1r7g]], [[1a1v\|1a1v]], [[1hei\|1hei]], [[1r7e\|1r7e]], [[1jr6\|1jr6]], [[2xi3\|2xi3]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xi2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xi2 RCSB], [http://www.ebi.ac.uk/pdbsum/2xi2 PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The hepatitis C virus (HCV) NS5b protein is an RNA-dependent RNA polymerase essential for replication of the viral RNA genome. In vitro and presumably in vivo, NS5b initiates RNA synthesis by a de novo mechanism. Different structural elements of NS5b have been reported to participate in RNA synthesis, especially a so-called "beta-flap" and a C-terminal segment (designated "linker") that connects the catalytic core of NS5b to a transmembrane anchor. High concentrations of GTP have also been shown to stimulate de novo RNA synthesis by HCV NS5b. Here we describe a combined structural and functional analysis of genotype 1 HCV-NS5b of strains H77 (subtype 1a), for which no structure has been previously reported, and J4 (subtype 1b). Our results highlight the linker as directly involved in lifting the first boundary to processive RNA synthesis, the formation of the first dinucleotide primer. The transition from this first dinucleotide primer state to processive RNA synthesis requires removal of the linker and of the beta-flap with which it is shown to strongly interact in crystal structures of HCV NS5b. We find that GTP specifically stimulates this transition irrespective of its incorporation in neosynthesized RNA.

-	~~{{STRUCTURE_2xi2\| PDB=2xi2 \| SCENE= }}~~	+	Further insights into the roles of GTP and the C terminus of the hepatitis C virus polymerase in the initiation of RNA synthesis.,Harrus D, Ahmed-El-Sayed N, Simister PC, Miller S, Triconnet M, Hagedorn CH, Mahias K, Rey FA, Astier-Gin T, Bressanelli S J Biol Chem. 2010 Oct 22;285(43):32906-18. Epub 2010 Aug 20. PMID:20729191<ref>PMID:20729191</ref>

-	~~===HCV-H77 NS5B APO POLYMERASE===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_20729191}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[2xi2]] is~~ a ~~3 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Hepatitis_c_virus Hepatitis c virus]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA].~~	+

	==See Also==		==See Also==
	*[[RNA polymerase\|RNA polymerase]]		*[[RNA polymerase\|RNA polymerase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:020729191<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Hepatitis c virus]]		[[Category: Hepatitis c virus]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]

OCA at 11:29, 20 October 2012

OCA — Sat, 20 Oct 2012 11:29:00 GMT

←Older revision		Revision as of 11:29, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[2xi2]] is a 3 chain structure ~~of [[RNA polymerase]]~~ with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA].	+	[[2xi2]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA].

	==See Also==		==See Also==

OCA at 05:32, 26 July 2012

OCA — Thu, 26 Jul 2012 05:32:39 GMT

←Older revision		Revision as of 05:32, 26 July 2012
Line 1:		Line 1:
	[[Image:2xi2.png\|left\|200px]]		[[Image:2xi2.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_2xi2", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_2xi2\| PDB=2xi2 \| SCENE= }}		{{STRUCTURE_2xi2\| PDB=2xi2 \| SCENE= }}

	===HCV-H77 NS5B APO POLYMERASE===		===HCV-H77 NS5B APO POLYMERASE===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_20729191}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 20729191 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_20729191}}		{{ABSTRACT_PUBMED_20729191}}

	==About this Structure==		==About this Structure==
-	[[2xi2]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA].	+	[[2xi2]] is a 3 chain structure of [[RNA polymerase]] with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XI2 OCA].
		+
		+	==See Also==
		+	*[[RNA polymerase\|RNA polymerase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~20729191~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:020729191</ref><references group="xtra"/>
	[[Category: Hepatitis c virus]]		[[Category: Hepatitis c virus]]
	[[Category: RNA-directed RNA polymerase]]		[[Category: RNA-directed RNA polymerase]]
Line 35:		Line 27:
	[[Category: Simister, P C.]]		[[Category: Simister, P C.]]
	[[Category: Triconnet, M.]]		[[Category: Triconnet, M.]]
		+	[[Category: De novo priming]]
		+	[[Category: Nonstructural protein]]
		+	[[Category: Rdrp]]
		+	[[Category: Replication]]
		+	[[Category: Transferase]]