7K9K

SARS-CoV-2 Spike RBD in complex with neutralizing Fab 2H04 (local refinement)

7K9K の概要

• エントリーDOI: 10.2210/pdb7k9k/pdb
• 関連するPDBエントリー: 7K9H 7K9I 7K9J
• EMDBエントリー: 22748 22749 22750 22751 22752 22753
• 分子名称: Spike protein S1, 2H04 heavy chain, 2H04 light chain, ... (4 entities in total)
• 機能のキーワード: sars-cov-2, neutralizing antibody, receptor-binding domain, viral protein-immune system complex, structural genomics, center for structural genomics of infectious diseases, csgid, viral protein/immune system
• 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: 47515.60

構造登録者

Errico, J.M.,Fremont, D.H.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2020-09-29, 公開日: 2021-09-29, 最終更新日: 2024-11-06)

主引用文献

Errico, J.M.,Zhao, H.,Chen, R.E.,Liu, Z.,Case, J.B.,Ma, M.,Schmitz, A.J.,Rau, M.J.,Fitzpatrick, J.A.J.,Shi, P.Y.,Diamond, M.S.,Whelan, S.P.J.,Ellebedy, A.H.,Fremont, D.H.
Structural mechanism of SARS-CoV-2 neutralization by two murine antibodies targeting the RBD.
Cell Rep, 37:109881-109881, 2021

PubMed Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has necessitated the rapid development of antibody-based therapies and vaccines as countermeasures. Here, we use cryoelectron microscopy (cryo-EM) to characterize two protective anti-SARS-CoV-2 murine monoclonal antibodies (mAbs) in complex with the spike protein, revealing similarities between epitopes targeted by human and murine B cells. The more neutralizing mAb, 2B04, binds the receptor-binding motif (RBM) of the receptor-binding domain (RBD) and competes with angiotensin-converting enzyme 2 (ACE2). By contrast, 2H04 binds adjacent to the RBM and does not compete for ACE2 binding. Naturally occurring sequence variants of SARS-CoV-2 and corresponding neutralization escape variants selected in vitro map to our structurally defined epitopes, suggesting that SARS-CoV-2 might evade therapeutic antibodies with a limited set of mutations, underscoring the importance of combination mAb therapeutics. Finally, we show that 2B04 neutralizes SARS-CoV-2 infection by preventing ACE2 engagement, whereas 2H04 reduces host cell attachment without directly disrupting ACE2-RBM interactions, providing distinct inhibitory mechanisms used by RBD-specific mAbs.

PubMed: 34655519
DOI: 10.1016/j.celrep.2021.109881

実験手法

ELECTRON MICROSCOPY (3.14 Å)