7P19

Crystal structure of SARS-CoV-2 RBD Q498Y complexed with human ACE2

7P19 の概要

• エントリーDOI: 10.2210/pdb7p19/pdb
• 分子名称: Processed angiotensin-converting enzyme 2, Spike protein S1, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: viral spike; angiotensin converting enzyme-ii; sars-cov-2; ace-2, viral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 187595.64

構造登録者

Erausquin, E.,Lopez-Sagaseta, J. (登録日: 2021-07-01, 公開日: 2022-07-13, 最終更新日: 2024-11-13)

主引用文献

Erausquin, E.,Glaser, F.,Fernandez-Recio, J.,Lopez-Sagaseta, J.
Structural bases for the higher adherence to ACE2 conferred by the SARS-CoV-2 spike Q498Y substitution.
Acta Crystallogr D Struct Biol, 78:1156-1170, 2022

PubMed Abstract: A remarkable number of SARS-CoV-2 variants and other as yet unmonitored lineages harbor amino-acid substitutions with the potential to modulate the interface between the spike receptor-binding domain (RBD) and its receptor ACE2. The naturally occurring Q498Y substitution, which is present in currently circulating SARS-CoV-2 variants, has drawn the attention of several investigations. While computational predictions and in vitro binding studies suggest that Q498Y increases the binding affinity of the spike protein for ACE2, experimental in vivo models of infection have shown that a triple mutant carrying the Q498Y replacement is fatal in mice. To accurately characterize the binding kinetics of the RBD Q498Y-ACE2 interaction, biolayer interferometry analyses were performed. A significant enhancement of the RBD-ACE2 binding affinity relative to a reference SARS-CoV-2 variant of concern carrying three simultaneous replacements was observed. In addition, the RBD Q498Y mutant bound to ACE2 was crystallized. Compared with the structure of its wild-type counterpart, the RBD Q498Y-ACE2 complex reveals the conservation of major hydrogen-bond interactions and a more populated, nonpolar set of contacts mediated by the bulky side chain of Tyr498 that collectively lead to this increase in binding affinity. In summary, these studies contribute to a deeper understanding of the impact of a relevant mutation present in currently circulating SARS-CoV-2 variants which might lead to stronger host-pathogen interactions.

PubMed: 36048155
DOI: 10.1107/S2059798322007677

実験手法

X-RAY DIFFRACTION (3.24 Å)