View source for 4wht


==Structure of the Hepatitis C virus envelope glycoprotein E2 antigenic region 412-423 bound to the broadly neutralizing antibody 3/11, P1 crystal form==
<StructureSection load='4wht' size='340' side='right'caption='[[4wht]], [[Resolution|resolution]] 2.22&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4wht]] is a 36 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_hominis Hepacivirus hominis] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WHT 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]] 2.22&#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=4wht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wht OCA], [https://pdbe.org/4wht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wht RCSB], [https://www.ebi.ac.uk/pdbsum/4wht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wht ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9WJJ4_9HEPC Q9WJJ4_9HEPC] 
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== Publication Abstract from PubMed ==
Neutralizing antibodies (nAbs) targeting glycoprotein E2 are important to control hepatitis C virus (HCV) infection. One conserved antigenic site (amino acids 412-423) is disordered in the reported E2 structure, but a synthetic peptide mimicking this site forms a beta-hairpin in complex with three independent nAbs. Our structure of the same peptide in complex with nAb 3/11 demonstrates a strikingly different extended conformation. We also show that residues 412-423 are essential for virus entry, but not for E2 folding. Together with the neutralizing capacity of the 3/11 Fab this indicates an unexpected structural flexibility within this epitope. NAbs 3/11 and AP33 (recognizing the extended and beta-hairpin conformation, respectively) display similar neutralizing activity despite converse binding kinetics. Our results suggest that HCV utilizes conformational flexibility as immune evasion strategy contributing to the limited immunogenicity of this epitope in patients, similar to the conformational flexibility described for other enveloped and non-enveloped viruses. IMPORTANCE: Approximately 180 million people worldwide are infected with Hepatitis C virus (HCV) and neutralizing antibodies play an important role in controlling replication of this major human pathogen. We show here that one of the most conserved antigenic sites within the major glycoprotein E2 (amino acids 412-423) - that is disordered in the recently reported crystal structure of an E2 core fragment - can adopt different conformations in the context of the infectious virus particle. Recombinant Fab fragments recognizing different conformations of this antigenic site have similar neutralization activity in spite of converse kinetic binding parameters. Of note, an antibody response targeting this antigenic region is less frequent than to other more immunogenic regions in E2. Our results suggest that the observed conformational flexibility in this conserved antigenic region contributes to the evasion of the humoral host immune response, facilitating chronicity and viral spread of HCV within an infected individual.

Structural Flexibility of a Conserved Broadly Neutralizing Epitope in Hepatitis C Virus Glycoprotein E2.,Meola A, Tarr AW, England P, Meredith LW, McClure CP, Foung SK, McKeating JA, Ball JK, Rey FA, Krey T J Virol. 2014 Dec 3. pii: JVI.02190-14. PMID:25473061<ref>PMID:25473061</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
<references/>
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</StructureSection>
[[Category: Hepacivirus hominis]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Krey T]]
[[Category: Rey FA]]