6nip - Revision history

OCA at 06:54, 11 October 2023

2023-10-11T06:54:33Z

←Older revision		Revision as of 06:54, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6nip' size='340' side='right'caption='[[6nip]], [[Resolution\|resolution]] 4.16Å' scene=''>		<StructureSection load='6nip' size='340' side='right'caption='[[6nip]], [[Resolution\|resolution]] 4.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nip]] is a 6 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~] and [~~http~~://en.wikipedia.org/wiki/~~Zikv Zikv~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NIP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6NIP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nip]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Zika_virus_ZIKV/H._sapiens/FrenchPolynesia/10087PF/2013 Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NIP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NIP FirstGlance]. <br>
-	</td></tr><tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~IGHV4~~-~~5908 (~~[~~http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN~~]~~), IGLV1-4401 ([http://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=9606 HUMAN])~~</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]] 4.16Å</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=6nip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nip OCA], [~~http~~://pdbe.org/6nip PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6nip RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6nip PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6nip 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=6nip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nip OCA], [https://pdbe.org/6nip PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nip RCSB], [https://www.ebi.ac.uk/pdbsum/6nip PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nip ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/POLG_ZIKVF POLG_ZIKVF]] Capsid protein C: Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome penetration into the host cytoplasm after hemifusion induced by the surface proteins. Can migrate to the cell nucleus where it modulates host functions.[UniProtKB:P17763] Capsid protein C: Inhibits RNA silencing by interfering with host Dicer.[UniProtKB:P03314] Peptide pr: Prevents premature fusion activity of envelope proteins in trans-Golgi by binding to envelope protein E at pH6.0. After virion release in extracellular space, gets dissociated from E dimers.[UniProtKB:P17763] Protein prM: Plays a role in host immune defense modulation and protection of envelope protein E during virion synthesis. PrM-E cleavage is ineficient, and immature prM-E proteins could have an activity against host immune response. The sequence of PrM contributes to fetal microcephaly in Humans. Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is the only viral peptide matured by host furin in the trans-Golgi network probably to avoid catastrophic activation of the viral fusion activity in acidic Golgi compartment prior to virion release. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM could play a role in immune evasion.[UniProtKB:P17763]<ref>PMID:28971967</ref> Small envelope protein M: May play a role in virus budding. Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M ectodomain. May display a viroporin activity.[UniProtKB:P17763] Envelope protein E: Binds to host cell surface receptor and mediates fusion between viral and cellular membranes. Envelope protein is synthesized in the endoplasmic reticulum in the form of heterodimer with protein prM. They play a role in virion budding in the ER, and the newly formed immature particule is covered with 60 spikes composed of heterodimer between precursor prM and envelope protein E. The virion is transported to the Golgi apparatus where the low pH causes dissociation of PrM-E heterodimers and formation of E homodimers. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM could play a role in immune evasion.[UniProtKB:P17763] Non-structural protein 1: Involved in immune evasion, pathogenesis and viral replication. Once cleaved off the polyprotein, is targeted to three destinations: the viral replication cycle, the plasma membrane and the extracellular compartment. Essential for viral replication. Required for formation of the replication complex and recruitment of other non-structural proteins to the ER-derived membrane structures. Excreted as a hexameric lipoparticle that plays a role against host immune response. Antagonizing the complement function. Binds to the host macrophages and dendritic cells. Inhibits signal transduction originating from Toll-like receptor 3 (TLR3).[UniProtKB:Q9Q6P4] Non-structural protein 2A: Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host alpha/beta interferon antiviral response (By similarity). Disrupts adherens junction formation and thereby impairs proliferation of radial cells in both embryonic mouse cortex and human forebrain organoids (PubMed:28826723).[UniProtKB:P14335]<ref>PMID:28826723</ref> Non-structural protein 2B: Required cofactor for the serine protease function of NS3.[UniProtKB:Q32ZE1] Serine protease NS3: Displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction (By similarity). Leads to translation arrest when expressed ex vivo (PubMed:28592527).[UniProtKB:Q32ZE1]<ref>PMID:28592527</ref> Non-structural protein 4A: Regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding (By similarity). Cooperatively with NS4B suppress the Akt-mTOR pathway and lead to cellular dysregulation (PubMed:27524440). Leads to translation arrest when expressed ex vivo (PubMed:28592527).[UniProtKB:Q9Q6P4]<ref>PMID:27524440</ref> <ref>PMID:28592527</ref> Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter. Non-structural protein 4B: Induces the formation of ER-derived membrane vesicles where the viral replication takes place. Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway. Inhibits STAT2 translocation in the nucleus after IFN-alpha treatment (By similarity). Cooperatively with NS4A suppress the Akt-mTOR pathway and lead to cellular dysregulation (PubMed:27524440).[UniProtKB:Q9Q6P4]<ref>PMID:27524440</ref> RNA-directed RNA polymerase NS5: Replicates the viral (+) and (-) RNA genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in RNA genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway.[UniProtKB:Q9Q6P4]	+	[https://www.uniprot.org/uniprot/POLG_ZIKVF POLG_ZIKVF] Capsid protein C: Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome penetration into the host cytoplasm after hemifusion induced by the surface proteins. Can migrate to the cell nucleus where it modulates host functions.[UniProtKB:P17763] Capsid protein C: Inhibits RNA silencing by interfering with host Dicer.[UniProtKB:P03314] Peptide pr: Prevents premature fusion activity of envelope proteins in trans-Golgi by binding to envelope protein E at pH6.0. After virion release in extracellular space, gets dissociated from E dimers.[UniProtKB:P17763] Protein prM: Plays a role in host immune defense modulation and protection of envelope protein E during virion synthesis. PrM-E cleavage is ineficient, and immature prM-E proteins could have an activity against host immune response. The sequence of PrM contributes to fetal microcephaly in Humans. Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is the only viral peptide matured by host furin in the trans-Golgi network probably to avoid catastrophic activation of the viral fusion activity in acidic Golgi compartment prior to virion release. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM could play a role in immune evasion.[UniProtKB:P17763]<ref>PMID:28971967</ref> Small envelope protein M: May play a role in virus budding. Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M ectodomain. May display a viroporin activity.[UniProtKB:P17763] Envelope protein E: Binds to host cell surface receptor and mediates fusion between viral and cellular membranes. Envelope protein is synthesized in the endoplasmic reticulum in the form of heterodimer with protein prM. They play a role in virion budding in the ER, and the newly formed immature particule is covered with 60 spikes composed of heterodimer between precursor prM and envelope protein E. The virion is transported to the Golgi apparatus where the low pH causes dissociation of PrM-E heterodimers and formation of E homodimers. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM could play a role in immune evasion.[UniProtKB:P17763] Non-structural protein 1: Involved in immune evasion, pathogenesis and viral replication. Once cleaved off the polyprotein, is targeted to three destinations: the viral replication cycle, the plasma membrane and the extracellular compartment. Essential for viral replication. Required for formation of the replication complex and recruitment of other non-structural proteins to the ER-derived membrane structures. Excreted as a hexameric lipoparticle that plays a role against host immune response. Antagonizing the complement function. Binds to the host macrophages and dendritic cells. Inhibits signal transduction originating from Toll-like receptor 3 (TLR3).[UniProtKB:Q9Q6P4] Non-structural protein 2A: Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host alpha/beta interferon antiviral response (By similarity). Disrupts adherens junction formation and thereby impairs proliferation of radial cells in both embryonic mouse cortex and human forebrain organoids (PubMed:28826723).[UniProtKB:P14335]<ref>PMID:28826723</ref> Non-structural protein 2B: Required cofactor for the serine protease function of NS3.[UniProtKB:Q32ZE1] Serine protease NS3: Displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction (By similarity). Leads to translation arrest when expressed ex vivo (PubMed:28592527).[UniProtKB:Q32ZE1]<ref>PMID:28592527</ref> Non-structural protein 4A: Regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding (By similarity). Cooperatively with NS4B suppress the Akt-mTOR pathway and lead to cellular dysregulation (PubMed:27524440). Leads to translation arrest when expressed ex vivo (PubMed:28592527).[UniProtKB:Q9Q6P4]<ref>PMID:27524440</ref> <ref>PMID:28592527</ref> Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter. Non-structural protein 4B: Induces the formation of ER-derived membrane vesicles where the viral replication takes place. Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway. Inhibits STAT2 translocation in the nucleus after IFN-alpha treatment (By similarity). Cooperatively with NS4A suppress the Akt-mTOR pathway and lead to cellular dysregulation (PubMed:27524440).[UniProtKB:Q9Q6P4]<ref>PMID:27524440</ref> RNA-directed RNA polymerase NS5: Replicates the viral (+) and (-) RNA genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in RNA genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway.[UniProtKB:Q9Q6P4]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6nip" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6nip" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Zikv~~]]	+	[[Category: Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013]]
-	[[Category: Choe, M]]	+	[[Category: Choe M]]
-	[[Category: Donofrio, G]]	+	[[Category: Donofrio G]]
-	[[Category: Dussupt, V]]	+	[[Category: Dussupt V]]
-	[[Category: Joyce~~, M G~~]]	+	[[Category: Joyce MG]]
-	[[Category: Krebs~~, S J~~]]	+	[[Category: Krebs SJ]]
-	[[Category: Michael~~, N L~~]]	+	[[Category: Michael NL]]
-	[[Category: Modjarrad, K]]	+	[[Category: Modjarrad K]]
-	[[Category: Sankhala~~, R S]]~~	+	[[Category: Sankhala RS]]
-	~~[[Category: Antibody]]~~	+
-	~~[[Category: Vaccination]]~~	+
-	~~[[Category: Viral protein-immune system complex]]~~	+
-	~~[[Category: Zikv-denv~~]]	+

OCA at 09:00, 6 January 2021

2021-01-06T09:00:48Z

←Older revision		Revision as of 09:00, 6 January 2021
Line 3:		Line 3:
	<StructureSection load='6nip' size='340' side='right'caption='[[6nip]], [[Resolution\|resolution]] 4.16Å' scene=''>		<StructureSection load='6nip' size='340' side='right'caption='[[6nip]], [[Resolution\|resolution]] 4.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nip]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NIP OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6NIP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nip]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Zikv Zikv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NIP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6NIP 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=6nip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nip OCA], [http://pdbe.org/6nip PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nip RCSB], [http://www.ebi.ac.uk/pdbsum/6nip PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nip ProSAT]</span></td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IGHV4-5908 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IGLV1-4401 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6nip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nip OCA], [http://pdbe.org/6nip PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nip RCSB], [http://www.ebi.ac.uk/pdbsum/6nip PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nip ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/POLG_ZIKVF POLG_ZIKVF]] Capsid protein C: Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome penetration into the host cytoplasm after hemifusion induced by the surface proteins. Can migrate to the cell nucleus where it modulates host functions.[UniProtKB:P17763] Capsid protein C: Inhibits RNA silencing by interfering with host Dicer.[UniProtKB:P03314] Peptide pr: Prevents premature fusion activity of envelope proteins in trans-Golgi by binding to envelope protein E at pH6.0. After virion release in extracellular space, gets dissociated from E dimers.[UniProtKB:P17763] Protein prM: Plays a role in host immune defense modulation and protection of envelope protein E during virion synthesis. PrM-E cleavage is ineficient, and immature prM-E proteins could have an activity against host immune response. The sequence of PrM contributes to fetal microcephaly in Humans. Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is the only viral peptide matured by host furin in the trans-Golgi network probably to avoid catastrophic activation of the viral fusion activity in acidic Golgi compartment prior to virion release. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM could play a role in immune evasion.[UniProtKB:P17763]<ref>PMID:28971967</ref> Small envelope protein M: May play a role in virus budding. Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M ectodomain. May display a viroporin activity.[UniProtKB:P17763] Envelope protein E: Binds to host cell surface receptor and mediates fusion between viral and cellular membranes. Envelope protein is synthesized in the endoplasmic reticulum in the form of heterodimer with protein prM. They play a role in virion budding in the ER, and the newly formed immature particule is covered with 60 spikes composed of heterodimer between precursor prM and envelope protein E. The virion is transported to the Golgi apparatus where the low pH causes dissociation of PrM-E heterodimers and formation of E homodimers. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM could play a role in immune evasion.[UniProtKB:P17763] Non-structural protein 1: Involved in immune evasion, pathogenesis and viral replication. Once cleaved off the polyprotein, is targeted to three destinations: the viral replication cycle, the plasma membrane and the extracellular compartment. Essential for viral replication. Required for formation of the replication complex and recruitment of other non-structural proteins to the ER-derived membrane structures. Excreted as a hexameric lipoparticle that plays a role against host immune response. Antagonizing the complement function. Binds to the host macrophages and dendritic cells. Inhibits signal transduction originating from Toll-like receptor 3 (TLR3).[UniProtKB:Q9Q6P4] Non-structural protein 2A: Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host alpha/beta interferon antiviral response (By similarity). Disrupts adherens junction formation and thereby impairs proliferation of radial cells in both embryonic mouse cortex and human forebrain organoids (PubMed:28826723).[UniProtKB:P14335]<ref>PMID:28826723</ref> Non-structural protein 2B: Required cofactor for the serine protease function of NS3.[UniProtKB:Q32ZE1] Serine protease NS3: Displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction (By similarity). Leads to translation arrest when expressed ex vivo (PubMed:28592527).[UniProtKB:Q32ZE1]<ref>PMID:28592527</ref> Non-structural protein 4A: Regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding (By similarity). Cooperatively with NS4B suppress the Akt-mTOR pathway and lead to cellular dysregulation (PubMed:27524440). Leads to translation arrest when expressed ex vivo (PubMed:28592527).[UniProtKB:Q9Q6P4]<ref>PMID:27524440</ref> <ref>PMID:28592527</ref> Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter. Non-structural protein 4B: Induces the formation of ER-derived membrane vesicles where the viral replication takes place. Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway. Inhibits STAT2 translocation in the nucleus after IFN-alpha treatment (By similarity). Cooperatively with NS4A suppress the Akt-mTOR pathway and lead to cellular dysregulation (PubMed:27524440).[UniProtKB:Q9Q6P4]<ref>PMID:27524440</ref> RNA-directed RNA polymerase NS5: Replicates the viral (+) and (-) RNA genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in RNA genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway.[UniProtKB:Q9Q6P4]		[[http://www.uniprot.org/uniprot/POLG_ZIKVF POLG_ZIKVF]] Capsid protein C: Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome penetration into the host cytoplasm after hemifusion induced by the surface proteins. Can migrate to the cell nucleus where it modulates host functions.[UniProtKB:P17763] Capsid protein C: Inhibits RNA silencing by interfering with host Dicer.[UniProtKB:P03314] Peptide pr: Prevents premature fusion activity of envelope proteins in trans-Golgi by binding to envelope protein E at pH6.0. After virion release in extracellular space, gets dissociated from E dimers.[UniProtKB:P17763] Protein prM: Plays a role in host immune defense modulation and protection of envelope protein E during virion synthesis. PrM-E cleavage is ineficient, and immature prM-E proteins could have an activity against host immune response. The sequence of PrM contributes to fetal microcephaly in Humans. Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is the only viral peptide matured by host furin in the trans-Golgi network probably to avoid catastrophic activation of the viral fusion activity in acidic Golgi compartment prior to virion release. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM could play a role in immune evasion.[UniProtKB:P17763]<ref>PMID:28971967</ref> Small envelope protein M: May play a role in virus budding. Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M ectodomain. May display a viroporin activity.[UniProtKB:P17763] Envelope protein E: Binds to host cell surface receptor and mediates fusion between viral and cellular membranes. Envelope protein is synthesized in the endoplasmic reticulum in the form of heterodimer with protein prM. They play a role in virion budding in the ER, and the newly formed immature particule is covered with 60 spikes composed of heterodimer between precursor prM and envelope protein E. The virion is transported to the Golgi apparatus where the low pH causes dissociation of PrM-E heterodimers and formation of E homodimers. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM could play a role in immune evasion.[UniProtKB:P17763] Non-structural protein 1: Involved in immune evasion, pathogenesis and viral replication. Once cleaved off the polyprotein, is targeted to three destinations: the viral replication cycle, the plasma membrane and the extracellular compartment. Essential for viral replication. Required for formation of the replication complex and recruitment of other non-structural proteins to the ER-derived membrane structures. Excreted as a hexameric lipoparticle that plays a role against host immune response. Antagonizing the complement function. Binds to the host macrophages and dendritic cells. Inhibits signal transduction originating from Toll-like receptor 3 (TLR3).[UniProtKB:Q9Q6P4] Non-structural protein 2A: Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host alpha/beta interferon antiviral response (By similarity). Disrupts adherens junction formation and thereby impairs proliferation of radial cells in both embryonic mouse cortex and human forebrain organoids (PubMed:28826723).[UniProtKB:P14335]<ref>PMID:28826723</ref> Non-structural protein 2B: Required cofactor for the serine protease function of NS3.[UniProtKB:Q32ZE1] Serine protease NS3: Displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction (By similarity). Leads to translation arrest when expressed ex vivo (PubMed:28592527).[UniProtKB:Q32ZE1]<ref>PMID:28592527</ref> Non-structural protein 4A: Regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding (By similarity). Cooperatively with NS4B suppress the Akt-mTOR pathway and lead to cellular dysregulation (PubMed:27524440). Leads to translation arrest when expressed ex vivo (PubMed:28592527).[UniProtKB:Q9Q6P4]<ref>PMID:27524440</ref> <ref>PMID:28592527</ref> Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter. Non-structural protein 4B: Induces the formation of ER-derived membrane vesicles where the viral replication takes place. Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway. Inhibits STAT2 translocation in the nucleus after IFN-alpha treatment (By similarity). Cooperatively with NS4A suppress the Akt-mTOR pathway and lead to cellular dysregulation (PubMed:27524440).[UniProtKB:Q9Q6P4]<ref>PMID:27524440</ref> RNA-directed RNA polymerase NS5: Replicates the viral (+) and (-) RNA genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in RNA genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway.[UniProtKB:Q9Q6P4]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Zika virus (ZIKV) has caused significant disease, with widespread cases of neurological pathology and congenital neurologic defects. Rapid vaccine development has led to a number of candidates capable of eliciting potent ZIKV-neutralizing antibodies (reviewed in refs. (1-3)). Despite advances in vaccine development, it remains unclear how ZIKV vaccination affects immune responses in humans with prior flavivirus immunity. Here we show that a single-dose immunization of ZIKV purified inactivated vaccine (ZPIV)(4-7) in a dengue virus (DENV)-experienced human elicited potent cross-neutralizing antibodies to both ZIKV and DENV. Using a unique ZIKV virion-based sorting strategy, we isolated and characterized multiple antibodies, including one termed MZ4, which targets a novel site of vulnerability centered on the Envelope (E) domain I/III linker region and protects mice from viremia and viral dissemination following ZIKV or DENV-2 challenge. These data demonstrate that Zika vaccination in a DENV-experienced individual can boost pre-existing flavivirus immunity and elicit protective responses against both ZIKV and DENV. ZPIV vaccination in Puerto Rican individuals with prior flavivirus experience yielded similar cross-neutralizing potency after a single vaccination, highlighting the potential benefit of ZIKV vaccination in flavivirus-endemic areas.
		+
		+	Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor.,Dussupt V, Sankhala RS, Gromowski GD, Donofrio G, De La Barrera RA, Larocca RA, Zaky W, Mendez-Rivera L, Choe M, Davidson E, McCracken MK, Brien JD, Abbink P, Bai H, Bryan AL, Bias CH, Berry IM, Botero N, Cook T, Doria-Rose NA, Escuer AGI, Frimpong JA, Geretz A, Hernandez M, Hollidge BS, Jian N, Kabra K, Leggat DJ, Liu J, Pinto AK, Rutvisuttinunt W, Setliff I, Tran U, Townsley S, Doranz BJ, Rolland M, McDermott AB, Georgiev IS, Thomas R, Robb ML, Eckels KH, Barranco E, Koren M, Smith DR, Jarman RG, George SL, Stephenson KE, Barouch DH, Modjarrad K, Michael NL, Joyce MG, Krebs SJ Nat Med. 2020 Feb;26(2):228-235. doi: 10.1038/s41591-019-0746-2. Epub 2020 Feb 3. PMID:32015557<ref>PMID:32015557</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6nip" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Zikv]]
	[[Category: Choe, M]]		[[Category: Choe, M]]
	[[Category: Donofrio, G]]		[[Category: Donofrio, G]]
Line 22:		Line 34:
	[[Category: Sankhala, R S]]		[[Category: Sankhala, R S]]
	[[Category: Antibody]]		[[Category: Antibody]]
-	[[Category: Human]]
	[[Category: Vaccination]]		[[Category: Vaccination]]
	[[Category: Viral protein-immune system complex]]		[[Category: Viral protein-immune system complex]]
	[[Category: Zikv-denv]]		[[Category: Zikv-denv]]

OCA at 09:08, 25 December 2019

2019-12-25T09:08:22Z

←Older revision		Revision as of 09:08, 25 December 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6nip is ~~ON HOLD~~ ~~until Paper Publication~~	+	==Crystal structure of a human anti-ZIKV-DENV neutralizing antibody MZ1 in complex with ZIKV E glycoprotein==
-		+	<StructureSection load='6nip' size='340' side='right'caption='[[6nip]], [[Resolution\|resolution]] 4.16Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6nip]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NIP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NIP FirstGlance]. <br>
-	~~Description~~:	+	</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=6nip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nip OCA], [http://pdbe.org/6nip PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nip RCSB], [http://www.ebi.ac.uk/pdbsum/6nip PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nip ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/POLG_ZIKVF POLG_ZIKVF]] Capsid protein C: Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome penetration into the host cytoplasm after hemifusion induced by the surface proteins. Can migrate to the cell nucleus where it modulates host functions.[UniProtKB:P17763] Capsid protein C: Inhibits RNA silencing by interfering with host Dicer.[UniProtKB:P03314] Peptide pr: Prevents premature fusion activity of envelope proteins in trans-Golgi by binding to envelope protein E at pH6.0. After virion release in extracellular space, gets dissociated from E dimers.[UniProtKB:P17763] Protein prM: Plays a role in host immune defense modulation and protection of envelope protein E during virion synthesis. PrM-E cleavage is ineficient, and immature prM-E proteins could have an activity against host immune response. The sequence of PrM contributes to fetal microcephaly in Humans. Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is the only viral peptide matured by host furin in the trans-Golgi network probably to avoid catastrophic activation of the viral fusion activity in acidic Golgi compartment prior to virion release. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM could play a role in immune evasion.[UniProtKB:P17763]<ref>PMID:28971967</ref> Small envelope protein M: May play a role in virus budding. Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M ectodomain. May display a viroporin activity.[UniProtKB:P17763] Envelope protein E: Binds to host cell surface receptor and mediates fusion between viral and cellular membranes. Envelope protein is synthesized in the endoplasmic reticulum in the form of heterodimer with protein prM. They play a role in virion budding in the ER, and the newly formed immature particule is covered with 60 spikes composed of heterodimer between precursor prM and envelope protein E. The virion is transported to the Golgi apparatus where the low pH causes dissociation of PrM-E heterodimers and formation of E homodimers. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM could play a role in immune evasion.[UniProtKB:P17763] Non-structural protein 1: Involved in immune evasion, pathogenesis and viral replication. Once cleaved off the polyprotein, is targeted to three destinations: the viral replication cycle, the plasma membrane and the extracellular compartment. Essential for viral replication. Required for formation of the replication complex and recruitment of other non-structural proteins to the ER-derived membrane structures. Excreted as a hexameric lipoparticle that plays a role against host immune response. Antagonizing the complement function. Binds to the host macrophages and dendritic cells. Inhibits signal transduction originating from Toll-like receptor 3 (TLR3).[UniProtKB:Q9Q6P4] Non-structural protein 2A: Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host alpha/beta interferon antiviral response (By similarity). Disrupts adherens junction formation and thereby impairs proliferation of radial cells in both embryonic mouse cortex and human forebrain organoids (PubMed:28826723).[UniProtKB:P14335]<ref>PMID:28826723</ref> Non-structural protein 2B: Required cofactor for the serine protease function of NS3.[UniProtKB:Q32ZE1] Serine protease NS3: Displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction (By similarity). Leads to translation arrest when expressed ex vivo (PubMed:28592527).[UniProtKB:Q32ZE1]<ref>PMID:28592527</ref> Non-structural protein 4A: Regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding (By similarity). Cooperatively with NS4B suppress the Akt-mTOR pathway and lead to cellular dysregulation (PubMed:27524440). Leads to translation arrest when expressed ex vivo (PubMed:28592527).[UniProtKB:Q9Q6P4]<ref>PMID:27524440</ref> <ref>PMID:28592527</ref> Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter. Non-structural protein 4B: Induces the formation of ER-derived membrane vesicles where the viral replication takes place. Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway. Inhibits STAT2 translocation in the nucleus after IFN-alpha treatment (By similarity). Cooperatively with NS4A suppress the Akt-mTOR pathway and lead to cellular dysregulation (PubMed:27524440).[UniProtKB:Q9Q6P4]<ref>PMID:27524440</ref> RNA-directed RNA polymerase NS5: Replicates the viral (+) and (-) RNA genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in RNA genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway.[UniProtKB:Q9Q6P4]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Choe, M]]
		+	[[Category: Donofrio, G]]
		+	[[Category: Dussupt, V]]
		+	[[Category: Joyce, M G]]
		+	[[Category: Krebs, S J]]
		+	[[Category: Michael, N L]]
		+	[[Category: Modjarrad, K]]
		+	[[Category: Sankhala, R S]]
		+	[[Category: Antibody]]
		+	[[Category: Human]]
		+	[[Category: Vaccination]]
		+	[[Category: Viral protein-immune system complex]]
		+	[[Category: Zikv-denv]]

OCA at 07:03, 1 May 2019

2019-05-01T07:03:05Z

←Older revision		Revision as of 07:03, 1 May 2019
Line 3:		Line 3:
	The entry 6nip is ON HOLD until Paper Publication		The entry 6nip is ON HOLD until Paper Publication

-	Authors: ~~Sankhala, R.S., Dussupt, V., Donofrio, G., Choe, M., Modjarrad, K., Michael, N.L., Krebs, S.J., Joyce, M.G.~~	+	Authors:

-	Description: ~~Crystal structure of a human anti-ZIKV-DENV neutralizing antibody MZ1 in complex with ZIKV E glycoprotein~~	+	Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Joyce, M.G]]
-	[[Category: Choe, M]]
-	[[Category: Donofrio, G]]
-	[[Category: Michael, N.L]]
-	[[Category: Dussupt, V]]
-	[[Category: Krebs, S.J]]
-	[[Category: Modjarrad, K]]
-	[[Category: Sankhala, R.S]]

OCA at 10:06, 13 March 2019

2019-03-13T10:06:50Z

←Older revision		Revision as of 10:06, 13 March 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6nip is ON HOLD	+	The entry 6nip is ON HOLD until Paper Publication

	Authors: Sankhala, R.S., Dussupt, V., Donofrio, G., Choe, M., Modjarrad, K., Michael, N.L., Krebs, S.J., Joyce, M.G.		Authors: Sankhala, R.S., Dussupt, V., Donofrio, G., Choe, M., Modjarrad, K., Michael, N.L., Krebs, S.J., Joyce, M.G.

OCA: Protected "6nip" [edit=sysop:move=sysop]

2019-01-09T05:04:02Z

Protected "6nip" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:04, 9 January 2019

OCA: New page: '''Unreleased structure''' The entry 6nip is ON HOLD Authors: Sankhala, R.S., Dussupt, V., Donofrio, G., Choe, M., Modjarrad, K., Michael, N.L., Krebs, S.J., Joyce, M.G. Description: C...

2019-01-09T05:04:01Z

New page: '''Unreleased structure''' The entry 6nip is ON HOLD Authors: Sankhala, R.S., Dussupt, V., Donofrio, G., Choe, M., Modjarrad, K., Michael, N.L., Krebs, S.J., Joyce, M.G. Description: C...

New page

'''Unreleased structure'''

The entry 6nip is ON HOLD

Authors: Sankhala, R.S., Dussupt, V., Donofrio, G., Choe, M., Modjarrad, K., Michael, N.L., Krebs, S.J., Joyce, M.G.

Description: Crystal structure of a human anti-ZIKV-DENV neutralizing antibody MZ1 in complex with ZIKV E glycoprotein
[[Category: Unreleased Structures]]
[[Category: Joyce, M.G]]
[[Category: Choe, M]]
[[Category: Donofrio, G]]
[[Category: Michael, N.L]]
[[Category: Dussupt, V]]
[[Category: Krebs, S.J]]
[[Category: Modjarrad, K]]
[[Category: Sankhala, R.S]]