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| <StructureSection load='6uym' size='340' side='right'caption='[[6uym]], [[Resolution|resolution]] 2.85Å' scene=''> | | <StructureSection load='6uym' size='340' side='right'caption='[[6uym]], [[Resolution|resolution]] 2.85Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <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> | | <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 [https://proteopedia.org/fgij/fg.htm?mol=6UYM FirstGlance]. <br> |
| </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> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.848Å</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> | | <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'>[https://proteopedia.org/fgij/fg.htm?mol=6uym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uym OCA], [https://pdbe.org/6uym PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uym RCSB], [https://www.ebi.ac.uk/pdbsum/6uym PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uym ProSAT]</span></td></tr> |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| 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.
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| 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>
| | ==See Also== |
| | | *[[Antibody 3D structures|Antibody 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6uym" style="background-color:#fffaf0;"></div>
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| == References == | |
| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Hcv]]
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| [[Category: Human]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Tzarum, N]] | | [[Category: Tzarum N]] |
| [[Category: Wilson, I A]] | | [[Category: Wilson IA]] |
| [[Category: Zhu, J]] | | [[Category: Zhu J]] |
| [[Category: Bnab]]
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| [[Category: Broadly neutralizing antibody]]
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| [[Category: E2 core]]
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| [[Category: Immune system]]
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| [[Category: Self-assembly nanoparticle]]
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| [[Category: Vaccine design]]
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| [[Category: Viral protein-immune system complex]]
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