7YA1

Cryo-EM structure of hACE2-bound SARS-CoV-2 Omicron spike protein with L371S, P373S and F375S mutations (local refinement)

7YA1 の概要

• エントリーDOI: 10.2210/pdb7ya1/pdb
• EMDBエントリー: 33699
• 分子名称: Angiotensin-converting enzyme 2, Spike protein S1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: sars-cov-2, omicron, spike protein, viral protein, hydrolase-viral protein complex, hydrolase/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: 92705.25

構造登録者

Zhao, Z.N.,Xie, Y.F.,Qi, J.X.,Gao, G.F. (登録日: 2022-06-27, 公開日: 2022-08-31, 最終更新日: 2025-06-25)

主引用文献

Zhao, Z.,Zhou, J.,Tian, M.,Huang, M.,Liu, S.,Xie, Y.,Han, P.,Bai, C.,Han, P.,Zheng, A.,Fu, L.,Gao, Y.,Peng, Q.,Li, Y.,Chai, Y.,Zhang, Z.,Zhao, X.,Song, H.,Qi, J.,Wang, Q.,Wang, P.,Gao, G.F.
Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape.
Nat Commun, 13:4958-4958, 2022

PubMed Abstract: Omicron SARS-CoV-2 is rapidly spreading worldwide. To delineate the impact of emerging mutations on spike's properties, we performed systematic structural analyses on apo Omicron spike and its complexes with human ACE2 or S309 neutralizing antibody (NAb) by cryo-EM. The Omicron spike preferentially adopts the one-RBD-up conformation both before and after ACE2 binding, which is in sharp contrast to the orchestrated conformational changes to create more up-RBDs upon ACE2 binding as observed in the prototype and other four variants of concern (VOCs). Furthermore, we found that S371L, S373P and S375F substitutions enhance the stability of the one-RBD-up conformation to prevent exposing more up-RBDs triggered by ACE2 binding. The increased stability of the one-RBD-up conformation restricts the accessibility of S304 NAb, which targets a cryptic epitope in the closed conformation, thus facilitating the immune evasion by Omicron. These results expand our understanding of Omicron spike's conformation, receptor binding and antibody evasion mechanism.

PubMed: 36002453
DOI: 10.1038/s41467-022-32665-7

実験手法

ELECTRON MICROSCOPY (3.11 Å)