4xvj - Revision history

OCA at 17:54, 26 April 2023

OCA — Wed, 26 Apr 2023 17:54:14 GMT

←Older revision		Revision as of 17:54, 26 April 2023
Line 3:		Line 3:
	<StructureSection load='4xvj' size='340' side='right'caption='[[4xvj]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4xvj' size='340' side='right'caption='[[4xvj]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4xvj]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XVJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4XVJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4xvj]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_C Hepacivirus C] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XVJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XVJ FirstGlance]. <br>
-	</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=4xvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xvj OCA], [~~http~~://pdbe.org/4xvj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4xvj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4xvj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4xvj ProSAT]</span></td></tr>	+	</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=4xvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xvj OCA], [https://pdbe.org/4xvj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xvj RCSB], [https://www.ebi.ac.uk/pdbsum/4xvj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xvj ProSAT]</span></td></tr>
	</table>		</table>
		+	== 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
	*[[Antibody 3D structures\|Antibody 3D structures]]		*[[Antibody 3D structures\|Antibody 3D structures]]
		+	*[[3D structures of human antibody\|3D structures of human antibody]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Hepacivirus C]]
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Li, Y]]	+	[[Category: Li Y]]
-	[[Category: Mariuzza~~, R A]]~~	+	[[Category: Mariuzza RA]]
-	~~[[Category: Antibody-antigen complex]]~~	+
-	~~[[Category: Immune system~~]]	+

OCA at 23:42, 5 June 2019

OCA — Wed, 05 Jun 2019 23:42:07 GMT

←Older revision		Revision as of 23:42, 5 June 2019
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	==STRUCTURE OF THE HEPATITIS C VIRUS ENVELOPE GLYCOPROTEIN E2 ANTIGENIC 2 REGION 412-423 BOUND TO THE BROADLY NEUTRALIZING ANTIBODY HC33.1==		==STRUCTURE OF THE HEPATITIS C VIRUS ENVELOPE GLYCOPROTEIN E2 ANTIGENIC 2 REGION 412-423 BOUND TO THE BROADLY NEUTRALIZING ANTIBODY HC33.1==
-	<StructureSection load='4xvj' size='340' side='right' caption='[[4xvj]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='4xvj' size='340' side='right'caption='[[4xvj]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4xvj]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XVJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4xvj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XVJ FirstGlance]. <br>
	</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=4xvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xvj OCA], [http://pdbe.org/4xvj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xvj RCSB], [http://www.ebi.ac.uk/pdbsum/4xvj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xvj ProSAT]</span></td></tr>		</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=4xvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xvj OCA], [http://pdbe.org/4xvj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xvj RCSB], [http://www.ebi.ac.uk/pdbsum/4xvj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xvj ProSAT]</span></td></tr>
	</table>		</table>
Line 15:		Line 15:
	</div>		</div>
	<div class="pdbe-citations 4xvj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4xvj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Li, Y]]		[[Category: Li, Y]]
	[[Category: Mariuzza, R A]]		[[Category: Mariuzza, R A]]
	[[Category: Antibody-antigen complex]]		[[Category: Antibody-antigen complex]]
	[[Category: Immune system]]		[[Category: Immune system]]

OCA at 09:23, 2 January 2017

OCA — Mon, 02 Jan 2017 09:23:46 GMT

←Older revision		Revision as of 09:23, 2 January 2017
Line 1:		Line 1:

-	==~~STUCTURE~~ OF THE HEPATITIS C VIRUS ENVELOPE GLYCOPROTEIN E2 ANTIGENIC 2 REGION 412-423 BOUND TO THE BROADLY NEUTRALIZING ANTIBODY HC33.1==	+	==STRUCTURE OF THE HEPATITIS C VIRUS ENVELOPE GLYCOPROTEIN E2 ANTIGENIC 2 REGION 412-423 BOUND TO THE BROADLY NEUTRALIZING ANTIBODY HC33.1==
	<StructureSection load='4xvj' size='340' side='right' caption='[[4xvj]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4xvj' size='340' side='right' caption='[[4xvj]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==

OCA at 07:54, 27 July 2016

OCA — Wed, 27 Jul 2016 07:54:43 GMT

←Older revision		Revision as of 07:54, 27 July 2016
Line 1:		Line 1:
		+
	==STUCTURE OF THE HEPATITIS C VIRUS ENVELOPE GLYCOPROTEIN E2 ANTIGENIC 2 REGION 412-423 BOUND TO THE BROADLY NEUTRALIZING ANTIBODY HC33.1==		==STUCTURE OF THE HEPATITIS C VIRUS ENVELOPE GLYCOPROTEIN E2 ANTIGENIC 2 REGION 412-423 BOUND TO THE BROADLY NEUTRALIZING ANTIBODY HC33.1==
	<StructureSection load='4xvj' size='340' side='right' caption='[[4xvj]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4xvj' size='340' side='right' caption='[[4xvj]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4xvj]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XVJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4xvj]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XVJ FirstGlance]. <br>
-	</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=4xvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xvj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xvj RCSB], [http://www.ebi.ac.uk/pdbsum/4xvj PDBsum]</span></td></tr>	+	</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=4xvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xvj OCA], [http://pdbe.org/4xvj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xvj RCSB], [http://www.ebi.ac.uk/pdbsum/4xvj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xvj ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 13:		Line 14:
	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 4xvj" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:00, 18 March 2015

OCA — Wed, 18 Mar 2015 12:00:18 GMT

←Older revision		Revision as of 12:00, 18 March 2015
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	</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=4xvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xvj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xvj RCSB], [http://www.ebi.ac.uk/pdbsum/4xvj PDBsum]</span></td></tr>		</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=4xvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xvj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xvj RCSB], [http://www.ebi.ac.uk/pdbsum/4xvj PDBsum]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. A challenge for HCV vaccine development is to identify conserved epitopes able to elicit protective antibodies against this highly diverse virus. Glycan shielding is a mechanism by which HCV masks such epitopes on its E2 envelope glycoprotein. Antibodies to the E2 region comprising residues 412-423 (E2412-423) have broadly neutralizing activities. However, an adaptive mutation in this linear epitope, Asn417Ser, is associated with a glycosylation shift from Asn417 to Asn415 that enables HCV to escape neutralization by monoclonal antibodies (mAbs) such as HCV1 and AP33. By contrast, the human mAb HC33.1 can neutralize virus bearing the Asn417Ser mutation. To understand how HC33.1 penetrates the glycan shield created by the glycosylation shift to Asn415, we determined the structure of this broadly neutralizing mAb in complex with its E2412-423 epitope to 2.0 A resolution. The conformation of E2412-423 bound to HC33.1 is distinct from the beta-hairpin conformation of this peptide bound to HCV1 or AP33, due to disruption of the beta-hairpin through interactions with the unusually long complementarity-determining region 3 (CDR3) of the HC33.1 heavy chain. Whereas Asn415 is buried by HCV1 and AP33, it is solvent-exposed in the HC33.1-E2412-423 complex, such that glycosylation of Asn415 would not prevent antibody binding. Furthermore, our results highlight the structural flexibility of the E2412-423 epitope, which may serve as an immune evasion strategy to impede induction of antibodies targeting this site by reducing its antigenicity.
		+
		+	Structural Basis for Penetration of the Glycan Shield of Hepatitis C Virus E2 Glycoprotein by a Broadly Neutralizing Human Antibody.,Li Y, Pierce BG, Wang Q, Keck ZY, Fuerst TR, Foung SK, Mariuzza RA J Biol Chem. 2015 Mar 3. pii: jbc.M115.643528. PMID:25737449<ref>PMID:25737449</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 12:00, 11 March 2015

OCA — Wed, 11 Mar 2015 12:00:54 GMT

←Older revision		Revision as of 12:00, 11 March 2015
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-	~~'''Unreleased structure'''~~	+	==STUCTURE OF THE HEPATITIS C VIRUS ENVELOPE GLYCOPROTEIN E2 ANTIGENIC 2 REGION 412-423 BOUND TO THE BROADLY NEUTRALIZING ANTIBODY HC33.1==
-		+	<StructureSection load='4xvj' size='340' side='right' caption='[[4xvj]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~The entry 4xvj is ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4xvj]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XVJ FirstGlance]. <br>
-	~~Authors: Li, Y., Mariuzza, R.A.~~	+	</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=4xvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xvj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xvj RCSB], [http://www.ebi.ac.uk/pdbsum/4xvj PDBsum]</span></td></tr>
-		+	</table>
-	~~Description:~~ STUCTURE OF THE HEPATITIS C VIRUS ENVELOPE GLYCOPROTEIN E2 ANTIGENIC 2 REGION 412-423 BOUND TO THE BROADLY NEUTRALIZING ANTIBODY HC33.1	+	__TOC__
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</StructureSection>
-	[[~~Category~~: ~~Mariuzza~~, R.A]]	+
	[[Category: Li, Y]]		[[Category: Li, Y]]
		+	[[Category: Mariuzza, R A]]
		+	[[Category: Antibody-antigen complex]]
		+	[[Category: Immune system]]

OCA at 09:51, 4 March 2015

OCA — Wed, 04 Mar 2015 09:51:01 GMT

←Older revision		Revision as of 09:51, 4 March 2015
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4xvj is ON HOLD	+	The entry 4xvj is ON HOLD until Paper Publication

	Authors: Li, Y., Mariuzza, R.A.		Authors: Li, Y., Mariuzza, R.A.

OCA at 10:45, 12 February 2015

OCA — Thu, 12 Feb 2015 10:45:24 GMT

←Older revision		Revision as of 10:45, 12 February 2015
Line 3:		Line 3:
	The entry 4xvj is ON HOLD		The entry 4xvj is ON HOLD

-	Authors: Li, Y, Mariuzza, R.A.	+	Authors: Li, Y., Mariuzza, R.A.

	Description: STUCTURE OF THE HEPATITIS C VIRUS ENVELOPE GLYCOPROTEIN E2 ANTIGENIC 2 REGION 412-423 BOUND TO THE BROADLY NEUTRALIZING ANTIBODY HC33.1		Description: STUCTURE OF THE HEPATITIS C VIRUS ENVELOPE GLYCOPROTEIN E2 ANTIGENIC 2 REGION 412-423 BOUND TO THE BROADLY NEUTRALIZING ANTIBODY HC33.1
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: ~~Li, Y,~~ Mariuzza, R.A]]	+	[[Category: Mariuzza, R.A]]
		+	[[Category: Li, Y]]

OCA: Protected "4xvj" [edit=sysop:move=sysop]

OCA — Sat, 07 Feb 2015 14:52:30 GMT

Protected "4xvj" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:52, 7 February 2015

OCA: New page: '''Unreleased structure''' The entry 4xvj is ON HOLD Authors: Li, Y, Mariuzza, R.A. Description: STUCTURE OF THE HEPATITIS C VIRUS ENVELOPE GLYCOPROTEIN E2 ANTIGENIC 2 REGION 412-423 B...

OCA — Sat, 07 Feb 2015 14:52:29 GMT

New page: '''Unreleased structure''' The entry 4xvj is ON HOLD Authors: Li, Y, Mariuzza, R.A. Description: STUCTURE OF THE HEPATITIS C VIRUS ENVELOPE GLYCOPROTEIN E2 ANTIGENIC 2 REGION 412-423 B...

New page

'''Unreleased structure'''

The entry 4xvj is ON HOLD

Authors: Li, Y, Mariuzza, R.A.

Description: STUCTURE OF THE HEPATITIS C VIRUS ENVELOPE GLYCOPROTEIN E2 ANTIGENIC 2 REGION 412-423 BOUND TO THE BROADLY NEUTRALIZING ANTIBODY HC33.1
[[Category: Unreleased Structures]]
[[Category: Li, Y, Mariuzza, R.A]]