7v2a: Difference between revisions
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==== | ==SARS-CoV-2 Spike trimer in complex with XG014 Fab== | ||
<StructureSection load='7v2a' size='340' side='right'caption='[[7v2a]]' scene=''> | <StructureSection load='7v2a' size='340' side='right'caption='[[7v2a]], [[Resolution|resolution]] 3.40Å' 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'>[[7v2a]] 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=7V2A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V2A 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=7v2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v2a OCA], [https://pdbe.org/7v2a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v2a RCSB], [https://www.ebi.ac.uk/pdbsum/7v2a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v2a ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4Å</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=7v2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v2a OCA], [https://pdbe.org/7v2a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v2a RCSB], [https://www.ebi.ac.uk/pdbsum/7v2a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v2a ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes beta-coronavirus lineage B (beta-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-beta-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against beta-CoV-B and newly emerging SARS-CoV-2 variants of concern. | |||
An ultrapotent pan-beta-coronavirus lineage B (beta-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope.,Liu Z, Xu W, Chen Z, Fu W, Zhan W, Gao Y, Zhou J, Zhou Y, Wu J, Wang Q, Zhang X, Hao A, Wu W, Zhang Q, Li Y, Fan K, Chen R, Jiang Q, Mayer CT, Schoofs T, Xie Y, Jiang S, Wen Y, Yuan Z, Wang K, Lu L, Sun L, Wang Q Protein Cell. 2022 Sep;13(9):655-675. doi: 10.1007/s13238-021-00871-6. Epub 2021 , Sep 23. PMID:34554412<ref>PMID:34554412</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7v2a" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Severe acute respiratory syndrome coronavirus 2]] | ||
[[Category: Pan L]] | |||
[[Category: Wang K]] | |||
[[Category: Wang X]] |
Latest revision as of 12:16, 17 October 2024
SARS-CoV-2 Spike trimer in complex with XG014 FabSARS-CoV-2 Spike trimer in complex with XG014 Fab
Structural highlights
Publication Abstract from PubMedNew threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes beta-coronavirus lineage B (beta-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-beta-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against beta-CoV-B and newly emerging SARS-CoV-2 variants of concern. An ultrapotent pan-beta-coronavirus lineage B (beta-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope.,Liu Z, Xu W, Chen Z, Fu W, Zhan W, Gao Y, Zhou J, Zhou Y, Wu J, Wang Q, Zhang X, Hao A, Wu W, Zhang Q, Li Y, Fan K, Chen R, Jiang Q, Mayer CT, Schoofs T, Xie Y, Jiang S, Wen Y, Yuan Z, Wang K, Lu L, Sun L, Wang Q Protein Cell. 2022 Sep;13(9):655-675. doi: 10.1007/s13238-021-00871-6. Epub 2021 , Sep 23. PMID:34554412[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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