7L7E

Crystal structure of SARS-CoV-2 spike RBD in complex with human monoclonal antibodies AZD8895 and AZD1061

7L7E の概要

• エントリーDOI: 10.2210/pdb7l7e/pdb
• 分子名称: heavy chain of human monoclonal antibody AZD8895, light chain of human monoclonal antibody Fab AZD8895, heavy chain of human monoclonal antibody Fab AZD1061, ... (8 entities in total)
• 機能のキーワード: sars-cov-2, spike protein, receptor binding domain, human monoclonal antibody, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 485421.52

構造登録者

Dong, J.,Crowe, J.E. (登録日: 2020-12-28, 公開日: 2021-09-01, 最終更新日: 2024-11-13)

主引用文献

Dong, J.,Zost, S.J.,Greaney, A.J.,Starr, T.N.,Dingens, A.S.,Chen, E.C.,Chen, R.E.,Case, J.B.,Sutton, R.E.,Gilchuk, P.,Rodriguez, J.,Armstrong, E.,Gainza, C.,Nargi, R.S.,Binshtein, E.,Xie, X.,Zhang, X.,Shi, P.Y.,Logue, J.,Weston, S.,McGrath, M.E.,Frieman, M.B.,Brady, T.,Tuffy, K.M.,Bright, H.,Loo, Y.M.,McTamney, P.M.,Esser, M.T.,Carnahan, R.H.,Diamond, M.S.,Bloom, J.D.,Crowe Jr., J.E.
Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail.
Nat Microbiol, 6:1233-1244, 2021

PubMed Abstract: Understanding the molecular basis for immune recognition of SARS-CoV-2 spike glycoprotein antigenic sites will inform the development of improved therapeutics. We determined the structures of two human monoclonal antibodies-AZD8895 and AZD1061-which form the basis of the investigational antibody cocktail AZD7442, in complex with the receptor-binding domain (RBD) of SARS-CoV-2 to define the genetic and structural basis of neutralization. AZD8895 forms an 'aromatic cage' at the heavy/light chain interface using germ line-encoded residues in complementarity-determining regions (CDRs) 2 and 3 of the heavy chain and CDRs 1 and 3 of the light chain. These structural features explain why highly similar antibodies (public clonotypes) have been isolated from multiple individuals. AZD1061 has an unusually long LCDR1; the HCDR3 makes interactions with the opposite face of the RBD from that of AZD8895. Using deep mutational scanning and neutralization escape selection experiments, we comprehensively mapped the crucial binding residues of both antibodies and identified positions of concern with regards to virus escape from antibody-mediated neutralization. Both AZD8895 and AZD1061 have strong neutralizing activity against SARS-CoV-2 and variants of concern with antigenic substitutions in the RBD. We conclude that germ line-encoded antibody features enable recognition of the SARS-CoV-2 spike RBD and demonstrate the utility of the cocktail AZD7442 in neutralizing emerging variant viruses.

PubMed: 34548634
DOI: 10.1038/s41564-021-00972-2

実験手法

X-RAY DIFFRACTION (3 Å)