7YE5

SARS-CoV-2 Spike (6P) in complex with 2 R1-32 Fabs

7YE5 の概要

• エントリーDOI: 10.2210/pdb7ye5/pdb
• EMDBエントリー: 33764
• 分子名称: Spike glycoprotein, Heavy chain of R1-32 Fab, Light chain of R1-32 Fab, ... (5 entities in total)
• 機能のキーワード: ace2, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 501646.05

構造登録者

Liu, B.,Gao, X.,Li, Z.,Chen, X.,He, J.,Chen, L.,Xiong, X. (登録日: 2022-07-05, 公開日: 2022-08-24, 最終更新日: 2024-10-23)

主引用文献

He, P.,Liu, B.,Gao, X.,Yan, Q.,Pei, R.,Sun, J.,Chen, Q.,Hou, R.,Li, Z.,Zhang, Y.,Zhao, J.,Sun, H.,Feng, B.,Wang, Q.,Yi, H.,Hu, P.,Li, P.,Zhang, Y.,Chen, Z.,Niu, X.,Zhong, X.,Jin, L.,Liu, X.,Qu, K.,Ciazynska, K.A.,Carter, A.P.,Briggs, J.A.G.,Chen, J.,Liu, J.,Chen, X.,He, J.,Chen, L.,Xiong, X.
SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope.
Nat Microbiol, 7:1635-1649, 2022

PubMed Abstract: Population antibody response is thought to be important in selection of virus variants. We report that SARS-CoV-2 infection elicits a population immune response that is mediated by a lineage of VH1-69 germline antibodies. A representative antibody R1-32 from this lineage was isolated. By cryo-EM, we show that it targets a semi-cryptic epitope in the spike receptor-binding domain. Binding to this non-ACE2 competing epitope results in spike destruction, thereby inhibiting virus entry. On the basis of epitope location, neutralization mechanism and analysis of antibody binding to spike variants, we propose that recurrent substitutions at 452 and 490 are associated with immune evasion of the identified population antibody response. These substitutions, including L452R (present in the Delta variant), disrupt interactions mediated by the VH1-69-specific hydrophobic HCDR2 to impair antibody-antigen association, enabling variants to escape. The first Omicron variants were sensitive to antibody R1-32 but subvariants that harbour L452R quickly emerged and spread. Our results provide insights into how SARS-CoV-2 variants emerge and evade host immune responses.

PubMed: 36151403
DOI: 10.1038/s41564-022-01235-4

実験手法

ELECTRON MICROSCOPY (6.75 Å)