7CHP

Crystal structure of SARS-CoV-2 antibody P5A-3C8 with RBD

7CHP の概要

• エントリーDOI: 10.2210/pdb7chp/pdb
• 分子名称: Spike protein S1, antibody P5A-3C8 heavy chain, antibody P5A-3C8 light chain, ... (5 entities in total)
• 機能のキーワード: spike, receptor binding domain, antibody, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 71664.98

構造登録者

Wang, X.,Zhang, L.,Ge, J.,Wang, R.,Zhang, Q. (登録日: 2020-07-06, 公開日: 2021-05-19, 最終更新日: 2024-10-09)

主引用文献

Zhang, Q.,Ju, B.,Ge, J.,Chan, J.F.,Cheng, L.,Wang, R.,Huang, W.,Fang, M.,Chen, P.,Zhou, B.,Song, S.,Shan, S.,Yan, B.,Zhang, S.,Ge, X.,Yu, J.,Zhao, J.,Wang, H.,Liu, L.,Lv, Q.,Fu, L.,Shi, X.,Yuen, K.Y.,Liu, L.,Wang, Y.,Chen, Z.,Zhang, L.,Wang, X.,Zhang, Z.
Potent and protective IGHV3-53/3-66 public antibodies and their shared escape mutant on the spike of SARS-CoV-2.
Nat Commun, 12:4210-4210, 2021

PubMed Abstract: Neutralizing antibodies (nAbs) to SARS-CoV-2 hold powerful potentials for clinical interventions against COVID-19 disease. However, their common genetic and biologic features remain elusive. Here we interrogate a total of 165 antibodies from eight COVID-19 patients, and find that potent nAbs from different patients have disproportionally high representation of IGHV3-53/3-66 usage, and therefore termed as public antibodies. Crystal structural comparison of these antibodies reveals they share similar angle of approach to RBD, overlap in buried surface and binding residues on RBD, and have substantial spatial clash with receptor angiotensin-converting enzyme-2 (ACE2) in binding to RBD. Site-directed mutagenesis confirms these common binding features although some minor differences are found. One representative antibody, P5A-3C8, demonstrates extraordinarily protective efficacy in a golden Syrian hamster model against SARS-CoV-2 infection. However, virus escape analysis identifies a single natural mutation in RBD, namely K417N found in B.1.351 variant from South Africa, abolished the neutralizing activity of these public antibodies. The discovery of public antibodies and shared escape mutation highlight the intricate relationship between antibody response and SARS-CoV-2, and provide critical reference for the development of antibody and vaccine strategies to overcome the antigenic variation of SARS-CoV-2.

PubMed: 34244522
DOI: 10.1038/s41467-021-24514-w

実験手法

X-RAY DIFFRACTION (2.357 Å)