7R10

Dissociated S1 domain of Alpha Variant SARS-CoV-2 Spike bound to ACE2

7R10 の概要

• エントリーDOI: 10.2210/pdb7r10/pdb
• EMDBエントリー: 14226
• 分子名称: Angiotensin-converting enzyme 2, Spike glycoprotein, ZINC ION, ... (4 entities in total)
• 機能のキーワード: spike, sars-cov-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: 2
• 化学式量合計: 219114.15

構造登録者

Benton, D.J.,Wrobel, A.G.,Gamblin, S.J. (登録日: 2022-02-02, 公開日: 2022-03-02, 最終更新日: 2024-10-23)

主引用文献

Wrobel, A.G.,Benton, D.J.,Roustan, C.,Borg, A.,Hussain, S.,Martin, S.R.,Rosenthal, P.B.,Skehel, J.J.,Gamblin, S.J.
Evolution of the SARS-CoV-2 spike protein in the human host.
Nat Commun, 13:1178-1178, 2022

PubMed Abstract: Recently emerged variants of SARS-CoV-2 contain in their surface spike glycoproteins multiple substitutions associated with increased transmission and resistance to neutralising antibodies. We have examined the structure and receptor binding properties of spike proteins from the B.1.1.7 (Alpha) and B.1.351 (Beta) variants to better understand the evolution of the virus in humans. Spikes of both variants have the same mutation, N501Y, in the receptor-binding domains. This substitution confers tighter ACE2 binding, dependent on the common earlier substitution, D614G. Each variant spike has acquired other key changes in structure that likely impact virus pathogenesis. The spike from the Alpha variant is more stable against disruption upon binding ACE2 receptor than all other spikes studied. This feature is linked to the acquisition of a more basic substitution at the S1-S2 furin site (also observed for the variants of concern Delta, Kappa, and Omicron) which allows for near-complete cleavage. In the Beta variant spike, the presence of a new substitution, K417N (also observed in the Omicron variant), in combination with the D614G, stabilises a more open spike trimer, a conformation required for receptor binding. Our observations suggest ways these viruses have evolved to achieve greater transmissibility in humans.

PubMed: 35246509
DOI: 10.1038/s41467-022-28768-w

実験手法

ELECTRON MICROSCOPY (4 Å)