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==Structure of Hepatitis C Virus Envelope Glycoprotein E2mc3-v6 redesigned core from genotype 1a bound to broadly neutralizing antibody AR3C== | ==Structure of Hepatitis C Virus Envelope Glycoprotein E2mc3-v6 redesigned core from genotype 1a bound to broadly neutralizing antibody AR3C== | ||
<StructureSection load='6uym' size='340' side='right'caption='[[6uym]]' scene=''> | <StructureSection load='6uym' size='340' side='right'caption='[[6uym]], [[Resolution|resolution]] 2.85Å' 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=6UYM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UYM FirstGlance]. <br> | <table><tr><td colspan='2'>[[6uym]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Hcv Hcv] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UYM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UYM FirstGlance]. <br> | ||
</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=6uym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uym OCA], [http://pdbe.org/6uym PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uym RCSB], [http://www.ebi.ac.uk/pdbsum/6uym PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uym ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[http://proteopedia.org/fgij/fg.htm?mol=6uym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uym OCA], [http://pdbe.org/6uym PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uym RCSB], [http://www.ebi.ac.uk/pdbsum/6uym PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uym ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 are responsible for cell entry, with E2 being the major target of neutralizing antibodies (NAbs). Here, we present a comprehensive strategy for B cell-based HCV vaccine development through E2 optimization and nanoparticle display. We redesigned variable region 2 in a truncated form (tVR2) on E2 cores derived from genotypes 1a and 6a, resulting in improved stability and antigenicity. Crystal structures of three optimized E2 cores with human cross-genotype NAbs (AR3s) revealed how the modified tVR2 stabilizes E2 without altering key neutralizing epitopes. We then displayed these E2 cores on 24- and 60-meric nanoparticles and achieved substantial yield and purity, as well as enhanced antigenicity. In mice, these nanoparticles elicited more effective NAb responses than soluble E2 cores. Next-generation sequencing (NGS) defined distinct B cell patterns associated with nanoparticle-induced antibody responses, which target the conserved neutralizing epitopes on E2 and cross-neutralize HCV genotypes. | |||
Proof of concept for rational design of hepatitis C virus E2 core nanoparticle vaccines.,He L, Tzarum N, Lin X, Shapero B, Sou C, Mann CJ, Stano A, Zhang L, Nagy K, Giang E, Law M, Wilson IA, Zhu J Sci Adv. 2020 Apr 15;6(16):eaaz6225. doi: 10.1126/sciadv.aaz6225. eCollection, 2020 Apr. PMID:32494617<ref>PMID:32494617</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6uym" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Hcv]] | |||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Tzarum N]] | [[Category: Tzarum, N]] | ||
[[Category: Wilson | [[Category: Wilson, I A]] | ||
[[Category: Zhu J]] | [[Category: Zhu, J]] | ||
[[Category: Bnab]] | |||
[[Category: Broadly neutralizing antibody]] | |||
[[Category: E2 core]] | |||
[[Category: Immune system]] | |||
[[Category: Self-assembly nanoparticle]] | |||
[[Category: Vaccine design]] | |||
[[Category: Viral protein-immune system complex]] | |||
Revision as of 13:44, 17 June 2020
Structure of Hepatitis C Virus Envelope Glycoprotein E2mc3-v6 redesigned core from genotype 1a bound to broadly neutralizing antibody AR3CStructure of Hepatitis C Virus Envelope Glycoprotein E2mc3-v6 redesigned core from genotype 1a bound to broadly neutralizing antibody AR3C
Structural highlights
Publication Abstract from PubMedHepatitis C virus (HCV) envelope glycoproteins E1 and E2 are responsible for cell entry, with E2 being the major target of neutralizing antibodies (NAbs). Here, we present a comprehensive strategy for B cell-based HCV vaccine development through E2 optimization and nanoparticle display. We redesigned variable region 2 in a truncated form (tVR2) on E2 cores derived from genotypes 1a and 6a, resulting in improved stability and antigenicity. Crystal structures of three optimized E2 cores with human cross-genotype NAbs (AR3s) revealed how the modified tVR2 stabilizes E2 without altering key neutralizing epitopes. We then displayed these E2 cores on 24- and 60-meric nanoparticles and achieved substantial yield and purity, as well as enhanced antigenicity. In mice, these nanoparticles elicited more effective NAb responses than soluble E2 cores. Next-generation sequencing (NGS) defined distinct B cell patterns associated with nanoparticle-induced antibody responses, which target the conserved neutralizing epitopes on E2 and cross-neutralize HCV genotypes. Proof of concept for rational design of hepatitis C virus E2 core nanoparticle vaccines.,He L, Tzarum N, Lin X, Shapero B, Sou C, Mann CJ, Stano A, Zhang L, Nagy K, Giang E, Law M, Wilson IA, Zhu J Sci Adv. 2020 Apr 15;6(16):eaaz6225. doi: 10.1126/sciadv.aaz6225. eCollection, 2020 Apr. PMID:32494617[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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