View source for 8dv6


==Zika virus envelope protein structure in complex with a potent Human mAb==
<StructureSection load='8dv6' size='340' side='right'caption='[[8dv6]], [[Resolution|resolution]] 3.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8dv6]] 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/Human/Cambodia/FSS13025/2010 Zika virus ZIKV/Human/Cambodia/FSS13025/2010]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DV6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DV6 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.38&#8491;</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=8dv6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dv6 OCA], [https://pdbe.org/8dv6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dv6 RCSB], [https://www.ebi.ac.uk/pdbsum/8dv6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dv6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A173AEF6_ZIKV A0A173AEF6_ZIKV] Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[ARBA:ARBA00003504]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We currently have an incomplete understanding of why only a fraction of human antibodies that bind to flaviviruses block infection of cells. Here we define the footprint of a strongly neutralizing human monoclonal antibody (mAb G9E) with Zika virus (ZIKV) by both X-ray crystallography and cryo-electron microscopy. Flavivirus envelope (E) glycoproteins are present as homodimers on the virion surface, and G9E bound to a quaternary structure epitope spanning both E protomers forming a homodimer. As G9E mainly neutralized ZIKV by blocking a step after viral attachment to cells, we tested if the neutralization mechanism of G9E was dependent on the mAb cross-linking E molecules and blocking low-pH triggered conformational changes required for viral membrane fusion. We introduced targeted mutations to the G9E paratope to create recombinant antibodies that bound to the ZIKV envelope without cross-linking E protomers. The G9E paratope mutants that bound to a restricted epitope on one protomer poorly neutralized ZIKV compared to the wild-type mAb, demonstrating that the neutralization mechanism depended on the ability of G9E to cross-link E proteins. In cell-free low pH triggered viral fusion assay, both wild-type G9E, and epitope restricted paratope mutant G9E bound to ZIKV but only the wild-type G9E blocked fusion. We propose that, beyond antibody binding strength, the ability of human antibodies to cross-link E-proteins is a critical determinant of flavivirus neutralization potency.

Structure and neutralization mechanism of a human antibody targeting a complex Epitope on Zika virus.,Adams C, Carbaugh DL, Shu B, Ng TS, Castillo IN, Bhowmik R, Segovia-Chumbez B, Puhl AC, Graham S, Diehl SA, Lazear HM, Lok SM, de Silva AM, Premkumar L PLoS Pathog. 2023 Jan 10;19(1):e1010814. doi: 10.1371/journal.ppat.1010814. , eCollection 2023 Jan. PMID:36626401<ref>PMID:36626401</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8dv6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Zika virus ZIKV/Human/Cambodia/FSS13025/2010]]
[[Category: Cameron A]]
[[Category: Premkumar L]]
[[Category: Puhl AC]]
[[Category: DeSilva AM]]