View source for 7mwx


==Structure of the core ectodomain of the hepatitis C virus envelope glycoprotein 2 with tamarin CD81==
<StructureSection load='7mwx' size='340' side='right'caption='[[7mwx]], [[Resolution|resolution]] 3.32&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7mwx]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_hominis Hepacivirus hominis], [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Saguinus_oedipus Saguinus oedipus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MWX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MWX 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]] 3.32&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7mwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mwx OCA], [https://pdbe.org/7mwx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mwx RCSB], [https://www.ebi.ac.uk/pdbsum/7mwx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mwx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A2I6PIY9_9HEPC A0A2I6PIY9_9HEPC] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Hepatitis C virus (HCV) infection is a causal agent of chronic liver disease, cirrhosis and hepatocellular carcinoma in humans, and afflicts more than 70 million people worldwide. The HCV envelope glycoproteins E1 and E2 are responsible for the binding of the virus to the host cell, but the exact entry process remains undetermined(1). The majority of broadly neutralizing antibodies block interaction between HCV E2 and the large extracellular loop (LEL) of the cellular receptor CD81 (CD81-LEL)(2). Here we show that low pH enhances the binding of CD81-LEL to E2, and we determine the crystal structure of E2 in complex with an antigen-binding fragment (2A12) and CD81-LEL (E2-2A12-CD81-LEL); E2 in complex with 2A12 (E2-2A12); and CD81-LEL alone. After binding CD81, residues 418-422 in E2 are displaced, which allows for the extension of an internal loop consisting of residues 520-539. Docking of the E2-CD81-LEL complex onto a membrane-embedded, full-length CD81 places the residues Tyr529 and Trp531 of E2 proximal to the membrane. Liposome flotation assays show that low pH and CD81-LEL increase the interaction of E2 with membranes, whereas structure-based mutants of Tyr529, Trp531 and Ile422 in the amino terminus of E2 abolish membrane binding. These data support a model in which acidification and receptor binding result in a conformational change in E2 in preparation for membrane fusion.

Structural insights into hepatitis C virus receptor binding and entry.,Kumar A, Hossain RA, Yost SA, Bu W, Wang Y, Dearborn AD, Grakoui A, Cohen JI, Marcotrigiano J Nature. 2021 Sep 15. pii: 10.1038/s41586-021-03913-5. doi:, 10.1038/s41586-021-03913-5. PMID:34526719<ref>PMID:34526719</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7mwx" style="background-color:#fffaf0;"></div>

==See Also==
*[[CD81|CD81]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Hepacivirus hominis]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Saguinus oedipus]]
[[Category: Bu W]]
[[Category: Cohen JI]]
[[Category: Dearborn AD]]
[[Category: Grakoui A]]
[[Category: Hossain RA]]
[[Category: Kumar A]]
[[Category: Marcotrigiano J]]
[[Category: Wang Y]]
[[Category: Yost SA]]