8zc3: Difference between revisions
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The | ==SARS-CoV-2 Omicron BA.4 spike trimer (6P) in complex with 3 D1F6 Fabs (1 RBD up)== | ||
<StructureSection load='8zc3' size='340' side='right'caption='[[8zc3]], [[Resolution|resolution]] 4.69Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8zc3]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ZC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZC3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.69Å</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=8zc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8zc3 OCA], [https://pdbe.org/8zc3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8zc3 RCSB], [https://www.ebi.ac.uk/pdbsum/8zc3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8zc3 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein continues to evolve antigenically, impacting antibody immunity. D1F6, an affinity-matured non-stereotypic VH1-2 antibody isolated from a patient infected with the SARS-CoV-2 ancestral strain, effectively neutralizes most Omicron variants tested, including XBB.1.5. We identify that D1F6 in the immunoglobulin G (IgG) form is able to overcome the effect of most Omicron mutations through its avidity-enhanced multivalent S-trimer binding. Cryo-electron microscopy (cryo-EM) and biochemical analyses show that three simultaneous epitope mutations are generally needed to substantially disrupt the multivalent S-trimer binding by D1F6 IgG. Antigenic mutations at spike positions 346, 444, and 445, which appeared in the latest variants, have little effect on D1F6 binding individually. However, these mutations are able to act synergistically with earlier Omicron mutations to impair neutralization by affecting the interaction between D1F6 IgG and the S-trimer. These results provide insight into the mechanism by which accumulated antigenic mutations facilitate evasion of affinity-matured antibodies. | |||
An unconventional VH1-2 antibody tolerates escape mutations and shows an antigenic hotspot on SARS-CoV-2 spike.,Liu B, Niu X, Deng Y, Zhang Z, Wang Y, Gao X, Liang H, Li Z, Wang Q, Cheng Y, Chen Q, Huang S, Pan Y, Su M, Lin X, Niu C, Chen Y, Yang W, Zhang Y, Yan Q, He J, Zhao J, Chen L, Xiong X Cell Rep. 2024 May 27;43(6):114265. doi: 10.1016/j.celrep.2024.114265. PMID:38805396<ref>PMID:38805396</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8zc3" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: He | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | |||
[[Category: Severe acute respiratory syndrome coronavirus 2]] | |||
[[Category: Chen Q]] | |||
[[Category: Gao X]] | |||
[[Category: He J]] | |||
[[Category: Li Z]] | |||
[[Category: Liu B]] | |||
[[Category: Xiong X]] | |||
Latest revision as of 08:28, 12 June 2024
SARS-CoV-2 Omicron BA.4 spike trimer (6P) in complex with 3 D1F6 Fabs (1 RBD up)SARS-CoV-2 Omicron BA.4 spike trimer (6P) in complex with 3 D1F6 Fabs (1 RBD up)
Structural highlights
Publication Abstract from PubMedThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein continues to evolve antigenically, impacting antibody immunity. D1F6, an affinity-matured non-stereotypic VH1-2 antibody isolated from a patient infected with the SARS-CoV-2 ancestral strain, effectively neutralizes most Omicron variants tested, including XBB.1.5. We identify that D1F6 in the immunoglobulin G (IgG) form is able to overcome the effect of most Omicron mutations through its avidity-enhanced multivalent S-trimer binding. Cryo-electron microscopy (cryo-EM) and biochemical analyses show that three simultaneous epitope mutations are generally needed to substantially disrupt the multivalent S-trimer binding by D1F6 IgG. Antigenic mutations at spike positions 346, 444, and 445, which appeared in the latest variants, have little effect on D1F6 binding individually. However, these mutations are able to act synergistically with earlier Omicron mutations to impair neutralization by affecting the interaction between D1F6 IgG and the S-trimer. These results provide insight into the mechanism by which accumulated antigenic mutations facilitate evasion of affinity-matured antibodies. An unconventional VH1-2 antibody tolerates escape mutations and shows an antigenic hotspot on SARS-CoV-2 spike.,Liu B, Niu X, Deng Y, Zhang Z, Wang Y, Gao X, Liang H, Li Z, Wang Q, Cheng Y, Chen Q, Huang S, Pan Y, Su M, Lin X, Niu C, Chen Y, Yang W, Zhang Y, Yan Q, He J, Zhao J, Chen L, Xiong X Cell Rep. 2024 May 27;43(6):114265. doi: 10.1016/j.celrep.2024.114265. PMID:38805396[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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