OCA at 12:03, 1 February 2024

OCA — Thu, 01 Feb 2024 12:03:13 GMT

←Older revision		Revision as of 12:03, 1 February 2024
Line 1:		Line 1:

-	====	+	==Crystal structure of Zika virus envelope glycoprotein in complex with the Fab fragment of the broadly neutralizing human antibody EDE1 C10==
-	<StructureSection load='7a3n' size='340' side='right'caption='[[7a3n]]' scene=''>	+	<StructureSection load='7a3n' size='340' side='right'caption='[[7a3n]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7a3n]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Zika_virus Zika virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A3N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A3N FirstGlance]. <br>
-	</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=7a3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a3n OCA], [https://pdbe.org/7a3n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a3n RCSB], [https://www.ebi.ac.uk/pdbsum/7a3n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a3n ProSAT]</span></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]] 2.1Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></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=7a3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a3n OCA], [https://pdbe.org/7a3n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a3n RCSB], [https://www.ebi.ac.uk/pdbsum/7a3n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a3n ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[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;">
		+	== Publication Abstract from PubMed ==
		+	The human monoclonal antibody C10 exhibits extraordinary cross-reactivity, potently neutralizing Zika virus (ZIKV) and the four serotypes of dengue virus (DENV1-DENV4). Here we describe a comparative structure-function analysis of C10 bound to the envelope (E) protein dimers of the five viruses it neutralizes. We demonstrate that the C10 Fab has high affinity for ZIKV and DENV1 but not for DENV2, DENV3, and DENV4. We further show that the C10 interaction with the latter viruses requires an E protein conformational landscape that limits binding to only one of the three independent epitopes per virion. This limited affinity is nevertheless counterbalanced by the particle's icosahedral organization, which allows two different dimers to be reached by both Fab arms of a C10 immunoglobulin. The epitopes' geometric distribution thus confers C10 its exceptional neutralization breadth. Our results highlight the importance not only of paratope/epitope complementarity but also the topological distribution for epitope-focused vaccine design.
		+
		+	The epitope arrangement on flavivirus particles contributes to Mab C10's extraordinary neutralization breadth across Zika and dengue viruses.,Sharma A, Zhang X, Dejnirattisai W, Dai X, Gong D, Wongwiwat W, Duquerroy S, Rouvinski A, Vaney MC, Guardado-Calvo P, Haouz A, England P, Sun R, Zhou ZH, Mongkolsapaya J, Screaton GR, Rey FA Cell. 2021 Dec 9;184(25):6052-6066.e18. doi: 10.1016/j.cell.2021.11.010. Epub, 2021 Nov 30. PMID:34852239<ref>PMID:34852239</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7a3n" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Monoclonal Antibodies 3D structures\|Monoclonal Antibodies 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Z-~~disk~~]]	+	[[Category: Zika virus]]
		+	[[Category: Duquerroy S]]
		+	[[Category: Guardado-Calvo P]]
		+	[[Category: Rey FA]]
		+	[[Category: Rouvinski A]]
		+	[[Category: Sharma A]]
		+	[[Category: Vaney MC]]

OCA at 09:52, 8 December 2021

OCA — Wed, 08 Dec 2021 09:52:50 GMT

←Older revision		Revision as of 09:52, 8 December 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7a3n ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7a3n' size='340' side='right'caption='[[7a3n]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=7a3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a3n OCA], [https://pdbe.org/7a3n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a3n RCSB], [https://www.ebi.ac.uk/pdbsum/7a3n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a3n ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 05:55, 21 April 2021

OCA — Wed, 21 Apr 2021 05:55:10 GMT

←Older revision		Revision as of 05:55, 21 April 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7a3n is ON HOLD	+	The entry 7a3n is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7a3n" [edit=sysop:move=sysop]

OCA — Wed, 26 Aug 2020 09:16:07 GMT

Protected "7a3n" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:16, 26 August 2020

OCA: New page: '''Unreleased structure''' The entry 7a3n is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 26 Aug 2020 09:16:06 GMT

New page: '''Unreleased structure''' The entry 7a3n is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7a3n is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7a3n - Revision history

OCA at 12:03, 1 February 2024

OCA at 09:52, 8 December 2021

OCA at 05:55, 21 April 2021

OCA: Protected "7a3n" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7a3n is ON HOLD Authors: Description: Category: Unreleased Structures