7KFY

Structural basis for a germline-biased antibody response to SARS-CoV-2 (RBD:C1A-F10 Fab)

7KFY の概要

• エントリーDOI: 10.2210/pdb7kfy/pdb
• 関連するPDBエントリー: 7KFV 7KFW 7KFX
• 分子名称: Spike glycoprotein, heavy chain of human antibody C1A-F10 Fab, light chain of human antibody C1A-F10 Fab, ... (5 entities in total)
• 機能のキーワード: covid-19, sars-cov-2, neutralizing antibody, affinity maturation, immune system, immune system-viral protein complex, immune system/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: 72791.25

構造登録者

Pan, J.,Abraham, J.,Clark, L.,Clark, S. (登録日: 2020-10-15, 公開日: 2020-12-02, 最終更新日: 2024-11-13)

主引用文献

Clark, S.A.,Clark, L.E.,Pan, J.,Coscia, A.,McKay, L.G.A.,Shankar, S.,Johnson, R.I.,Griffiths, A.,Abraham, J.
Molecular basis for a germline-biased neutralizing antibody response to SARS-CoV-2.
Biorxiv, 2020

PubMed Abstract: The SARS-CoV-2 viral spike (S) protein mediates attachment and entry into host cells and is a major target of vaccine and drug design. Potent SARS-CoV-2 neutralizing antibodies derived from closely related antibody heavy chain genes (IGHV3-53 or 3-66) have been isolated from multiple COVID-19 convalescent individuals. These usually contain minimal somatic mutations and bind the S receptor-binding domain (RBD) to interfere with attachment to the cellular receptor angiotensin-converting enzyme 2 (ACE2). We used antigen-specific single B cell sorting to isolate S-reactive monoclonal antibodies from the blood of a COVID-19 convalescent individual. The seven most potent neutralizing antibodies were somatic variants of the same IGHV3-53-derived antibody and bind the RBD with varying affinity. We report X-ray crystal structures of four Fab variants bound to the RBD and use the structures to explain the basis for changes in RBD affinity. We show that a germline revertant antibody binds tightly to the SARS-CoV-2 RBD and neutralizes virus, and that gains in affinity for the RBD do not necessarily correlate with increased neutralization potency, suggesting that somatic mutation is not required to exert robust antiviral effect. Our studies clarify the molecular basis for a heavily germline-biased human antibody response to SARS-CoV-2.

PubMed: 33200128
DOI: 10.1101/2020.11.13.381533

実験手法

X-RAY DIFFRACTION (2.157 Å)