7rfc: Difference between revisions
No edit summary |
No edit summary |
||
| (One intermediate revision by the same user not shown) | |||
| Line 1: | Line 1: | ||
==== | ==Crystal structure of broadly neutralizing antibody mAb1382 in complex with Hepatitis C virus envelope glycoprotein E2 ectodomain== | ||
<StructureSection load='7rfc' size='340' side='right'caption='[[7rfc]]' scene=''> | <StructureSection load='7rfc' size='340' side='right'caption='[[7rfc]], [[Resolution|resolution]] 3.24Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7rfc]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_hominis Hepacivirus hominis] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RFC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RFC FirstGlance]. <br> | ||
</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=7rfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rfc OCA], [https://pdbe.org/7rfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rfc RCSB], [https://www.ebi.ac.uk/pdbsum/7rfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rfc 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]] 3.24Å</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=MAN:ALPHA-D-MANNOSE'>MAN</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=7rfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rfc OCA], [https://pdbe.org/7rfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rfc RCSB], [https://www.ebi.ac.uk/pdbsum/7rfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rfc ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The high genetic diversity of hepatitis C virus (HCV) complicates effective vaccine development. We screened a cohort of 435 HCV-infected individuals and found that 2%-5% demonstrated outstanding HCV-neutralizing activity. From four of these patients, we isolated 310 HCV antibodies, including neutralizing antibodies with exceptional breadth and potency. High neutralizing activity was enabled by the use of the VH1-69 heavy-chain gene segment, somatic mutations within CDRH1, and CDRH2 hydrophobicity. Structural and mutational analyses revealed an important role for mutations replacing the serines at positions 30 and 31, as well as the presence of neutral and hydrophobic residues at the tip of the CDRH3. Based on these characteristics, we computationally created a de novo antibody with a fully synthetic VH1-69 heavy chain that efficiently neutralized multiple HCV genotypes. Our findings provide a deep understanding of the generation of broadly HCV-neutralizing antibodies that can guide the design of effective vaccine candidates. | |||
Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization.,Weber T, Potthoff J, Bizu S, Labuhn M, Dold L, Schoofs T, Horning M, Ercanoglu MS, Kreer C, Gieselmann L, Vanshylla K, Langhans B, Janicki H, Stroh LJ, Knops E, Nierhoff D, Spengler U, Kaiser R, Bjorkman PJ, Krey T, Bankwitz D, Pfeifer N, Pietschmann T, Flyak AI, Klein F Immunity. 2022 Feb 8;55(2):341-354.e7. doi: 10.1016/j.immuni.2021.12.003. Epub , 2022 Jan 5. PMID:34990590<ref>PMID:34990590</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7rfc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Hepacivirus hominis]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Bjorkman PJ]] | ||
[[Category: Flyak AI]] | |||
Latest revision as of 12:34, 9 October 2024
Crystal structure of broadly neutralizing antibody mAb1382 in complex with Hepatitis C virus envelope glycoprotein E2 ectodomainCrystal structure of broadly neutralizing antibody mAb1382 in complex with Hepatitis C virus envelope glycoprotein E2 ectodomain
Structural highlights
Publication Abstract from PubMedThe high genetic diversity of hepatitis C virus (HCV) complicates effective vaccine development. We screened a cohort of 435 HCV-infected individuals and found that 2%-5% demonstrated outstanding HCV-neutralizing activity. From four of these patients, we isolated 310 HCV antibodies, including neutralizing antibodies with exceptional breadth and potency. High neutralizing activity was enabled by the use of the VH1-69 heavy-chain gene segment, somatic mutations within CDRH1, and CDRH2 hydrophobicity. Structural and mutational analyses revealed an important role for mutations replacing the serines at positions 30 and 31, as well as the presence of neutral and hydrophobic residues at the tip of the CDRH3. Based on these characteristics, we computationally created a de novo antibody with a fully synthetic VH1-69 heavy chain that efficiently neutralized multiple HCV genotypes. Our findings provide a deep understanding of the generation of broadly HCV-neutralizing antibodies that can guide the design of effective vaccine candidates. Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization.,Weber T, Potthoff J, Bizu S, Labuhn M, Dold L, Schoofs T, Horning M, Ercanoglu MS, Kreer C, Gieselmann L, Vanshylla K, Langhans B, Janicki H, Stroh LJ, Knops E, Nierhoff D, Spengler U, Kaiser R, Bjorkman PJ, Krey T, Bankwitz D, Pfeifer N, Pietschmann T, Flyak AI, Klein F Immunity. 2022 Feb 8;55(2):341-354.e7. doi: 10.1016/j.immuni.2021.12.003. Epub , 2022 Jan 5. PMID:34990590[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||