7fcp: Difference between revisions
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The entry | ==Crystallographic structure of two neutralizing antibodies in complex with SARS-CoV-2 spike receptor-binding Domain (RBD)== | ||
<StructureSection load='7fcp' size='340' side='right'caption='[[7fcp]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7fcp]] is a 5 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=7FCP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FCP FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=7fcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fcp OCA], [https://pdbe.org/7fcp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fcp RCSB], [https://www.ebi.ac.uk/pdbsum/7fcp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fcp ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Many SARS-CoV-2 neutralizing antibodies (nAbs) lose potency against variants of concern. In this study, we developed 2 strategies to produce mutation-resistant antibodies. First, a yeast library expressing mutant receptor binding domains (RBDs) of the spike protein was utilized to screen for potent nAbs that are least susceptible to viral escape. Among the candidate antibodies, P5-22 displayed ultrahigh potency for virus neutralization as well as an outstanding mutation resistance profile. Additionally, P14-44 and P15-16 were recognized as mutation-resistant antibodies with broad betacoronavirus neutralization properties. P15-16 has only 1 binding hotspot, which is K378 in the RBD of SARS-CoV-2. The crystal structure of the P5-22, P14-44, and RBD ternary complex clarified the unique mechanisms that underlie the excellent mutation resistance profiles of these antibodies. Secondly, polymeric IgG enhanced antibody avidity by eliminating P5-22's only hotspot, residue F486 in the RBD, thereby potently blocking cell entry by mutant viruses. Structural and functional analyses of antibodies screened using both potency assays and the yeast RBD library revealed rare, ultrapotent, mutation-resistant nAbs against SARS-CoV-2. | |||
Ultrapotent neutralizing antibodies against SARS-CoV-2 with a high degree of mutation resistance.,Zou J, Li L, Zheng P, Liang W, Hu S, Zhou S, Wang Y, Zhao J, Yuan D, Liu L, Wu D, Xu M, Zhang F, Zhu M, Wu Z, Cao X, Ni M, Ling X, Wu Y, Kuang Z, Hu M, Li J, Li X, Guo X, Xu T, Jiang H, Gao C, Yu M, Liu J, Zhong N, Zhou J, Huang JA, Jin T, He J J Clin Invest. 2022 Feb 15;132(4):e154987. doi: 10.1172/JCI154987. PMID:35108220<ref>PMID:35108220</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7fcp" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Spike protein 3D structures|Spike protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Severe acute respiratory syndrome coronavirus 2]] | |||
[[Category: Jin T]] | |||
[[Category: Zheng P]] | |||
Latest revision as of 11:43, 17 October 2024
Crystallographic structure of two neutralizing antibodies in complex with SARS-CoV-2 spike receptor-binding Domain (RBD)Crystallographic structure of two neutralizing antibodies in complex with SARS-CoV-2 spike receptor-binding Domain (RBD)
Structural highlights
Publication Abstract from PubMedMany SARS-CoV-2 neutralizing antibodies (nAbs) lose potency against variants of concern. In this study, we developed 2 strategies to produce mutation-resistant antibodies. First, a yeast library expressing mutant receptor binding domains (RBDs) of the spike protein was utilized to screen for potent nAbs that are least susceptible to viral escape. Among the candidate antibodies, P5-22 displayed ultrahigh potency for virus neutralization as well as an outstanding mutation resistance profile. Additionally, P14-44 and P15-16 were recognized as mutation-resistant antibodies with broad betacoronavirus neutralization properties. P15-16 has only 1 binding hotspot, which is K378 in the RBD of SARS-CoV-2. The crystal structure of the P5-22, P14-44, and RBD ternary complex clarified the unique mechanisms that underlie the excellent mutation resistance profiles of these antibodies. Secondly, polymeric IgG enhanced antibody avidity by eliminating P5-22's only hotspot, residue F486 in the RBD, thereby potently blocking cell entry by mutant viruses. Structural and functional analyses of antibodies screened using both potency assays and the yeast RBD library revealed rare, ultrapotent, mutation-resistant nAbs against SARS-CoV-2. Ultrapotent neutralizing antibodies against SARS-CoV-2 with a high degree of mutation resistance.,Zou J, Li L, Zheng P, Liang W, Hu S, Zhou S, Wang Y, Zhao J, Yuan D, Liu L, Wu D, Xu M, Zhang F, Zhu M, Wu Z, Cao X, Ni M, Ling X, Wu Y, Kuang Z, Hu M, Li J, Li X, Guo X, Xu T, Jiang H, Gao C, Yu M, Liu J, Zhong N, Zhou J, Huang JA, Jin T, He J J Clin Invest. 2022 Feb 15;132(4):e154987. doi: 10.1172/JCI154987. PMID:35108220[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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