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| - | ==Broadly neutralizing antibodies against HCV use a CDRH3 disulfide motif to recognize an E2 glycoprotein site that can be targeted for vaccine design== | + | ==Crystal structure of human monoclonal antibody HEPC46== |
| - | <StructureSection load='6meg' size='340' side='right' caption='[[6meg]], [[Resolution|resolution]] 1.41Å' scene=''> | + | <StructureSection load='6meg' size='340' side='right'caption='[[6meg]], [[Resolution|resolution]] 1.41Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6meg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MEG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MEG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6meg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MEG FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6meg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6meg OCA], [http://pdbe.org/6meg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6meg RCSB], [http://www.ebi.ac.uk/pdbsum/6meg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6meg ProSAT]</span></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]] 1.41Å</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=6meg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6meg OCA], [https://pdbe.org/6meg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6meg RCSB], [https://www.ebi.ac.uk/pdbsum/6meg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6meg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6meg" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6meg" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | + | *[[Sandbox 20009|Sandbox 20009]] |
| | + | *[[3D structures of human antibody|3D structures of human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bjorkman, P J]] | + | [[Category: Large Structures]] |
| - | [[Category: Flyak, A I]] | + | [[Category: Bjorkman PJ]] |
| - | [[Category: Broadly neutralizing antibody]] | + | [[Category: Flyak AI]] |
| - | [[Category: Hcv glycoprotein]]
| + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
Publication Abstract from PubMed
Hepatitis C virus (HCV) vaccine efforts are hampered by the extensive genetic diversity of HCV envelope glycoproteins E1 and E2. Structures of broadly neutralizing antibodies (bNAbs) (e.g., HEPC3, HEPC74) isolated from individuals who spontaneously cleared HCV infection facilitate immunogen design to elicit antibodies against multiple HCV variants. However, challenges in expressing HCV glycoproteins previously limited bNAb-HCV structures to complexes with truncated E2 cores. Here we describe crystal structures of full-length E2 ectodomain complexes with HEPC3 and HEPC74, revealing lock-and-key antibody-antigen interactions, E2 regions (including a target of immunogen design) that were truncated or disordered in E2 cores, and an antibody CDRH3 disulfide motif that exhibits common interactions with a conserved epitope despite different bNAb-E2 binding orientations. The structures display unusual features relevant to common genetic signatures of HCV bNAbs and demonstrate extraordinary plasticity in antibody-antigen interactions. In addition, E2 variants that bind HEPC3/HEPC74-like germline precursors may represent candidate vaccine immunogens.
HCV Broadly Neutralizing Antibodies Use a CDRH3 Disulfide Motif to Recognize an E2 Glycoprotein Site that Can Be Targeted for Vaccine Design.,Flyak AI, Ruiz S, Colbert MD, Luong T, Crowe JE Jr, Bailey JR, Bjorkman PJ Cell Host Microbe. 2018 Nov 14;24(5):703-716.e3. doi: 10.1016/j.chom.2018.10.009. PMID:30439340[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Flyak AI, Ruiz S, Colbert MD, Luong T, Crowe JE Jr, Bailey JR, Bjorkman PJ. HCV Broadly Neutralizing Antibodies Use a CDRH3 Disulfide Motif to Recognize an E2 Glycoprotein Site that Can Be Targeted for Vaccine Design. Cell Host Microbe. 2018 Nov 14;24(5):703-716.e3. doi: 10.1016/j.chom.2018.10.009. PMID:30439340 doi:http://dx.doi.org/10.1016/j.chom.2018.10.009
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