7dk4: Difference between revisions
New page: ==== <StructureSection load='7dk4' size='340' side='right'caption='7dk4' scene=''> == Structural highlights == <table><tr><td colspan='2'>Full crystallographic information is availabl... |
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==== | ==S-2H2-F3a structure, two RBDs are up and one RBD is down, each RBD binds with a 2H2 Fab.== | ||
<StructureSection load='7dk4' size='340' side='right'caption='[[7dk4]]' scene=''> | <StructureSection load='7dk4' size='340' side='right'caption='[[7dk4]], [[Resolution|resolution]] 3.80Å' 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 [ | <table><tr><td colspan='2'>[[7dk4]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] 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=7DK4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DK4 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.8Å</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=7dk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dk4 OCA], [https://pdbe.org/7dk4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dk4 RCSB], [https://www.ebi.ac.uk/pdbsum/7dk4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dk4 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 A resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections. | |||
Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections.,Zhang C, Wang Y, Zhu Y, Liu C, Gu C, Xu S, Wang Y, Zhou Y, Wang Y, Han W, Hong X, Yang Y, Zhang X, Wang T, Xu C, Hong Q, Wang S, Zhao Q, Qiao W, Zang J, Kong L, Wang F, Wang H, Qu D, Lavillette D, Tang H, Deng Q, Xie Y, Cong Y, Huang Z Nat Commun. 2021 Jan 11;12(1):264. doi: 10.1038/s41467-020-20465-w. PMID:33431876<ref>PMID:33431876</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7dk4" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Severe acute respiratory syndrome coronavirus 2]] | |||
[[Category: Cong Y]] | |||
[[Category: Wang YF]] | |||
Latest revision as of 11:40, 17 October 2024
S-2H2-F3a structure, two RBDs are up and one RBD is down, each RBD binds with a 2H2 Fab.S-2H2-F3a structure, two RBDs are up and one RBD is down, each RBD binds with a 2H2 Fab.
Structural highlights
Publication Abstract from PubMedThe ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 A resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections. Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections.,Zhang C, Wang Y, Zhu Y, Liu C, Gu C, Xu S, Wang Y, Zhou Y, Wang Y, Han W, Hong X, Yang Y, Zhang X, Wang T, Xu C, Hong Q, Wang S, Zhao Q, Qiao W, Zang J, Kong L, Wang F, Wang H, Qu D, Lavillette D, Tang H, Deng Q, Xie Y, Cong Y, Huang Z Nat Commun. 2021 Jan 11;12(1):264. doi: 10.1038/s41467-020-20465-w. PMID:33431876[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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