8T22

Cryo-EM structure of mink variant Y453F trimeric spike protein bound to one mink ACE2 receptors at downRBD conformation

これはPDB形式変換不可エントリーです。

8T22 の概要

• エントリーDOI: 10.2210/pdb8t22/pdb
• EMDBエントリー: 40978
• 分子名称: Spike glycoprotein, Angiotensin-converting enzyme (2 entities in total)
• 機能のキーワード: coronavirus, spike, ace2, mink, protein binding, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 510107.83

構造登録者

Ahn, H.M.,Calderon, B.,Fan, X.,Gao, Y.,Horgan, N.,Zhou, B.,Liang, B. (登録日: 2023-06-05, 公開日: 2023-10-25, 最終更新日: 2024-10-23)

主引用文献

Ahn, H.,Calderon, B.M.,Fan, X.,Gao, Y.,Horgan, N.L.,Jiang, N.,Blohm, D.S.,Hossain, J.,Rayyan, N.W.K.,Osman, S.H.,Lin, X.,Currier, M.,Steel, J.,Wentworth, D.E.,Zhou, B.,Liang, B.
Structural basis of the American mink ACE2 binding by Y453F trimeric spike glycoproteins of SARS-CoV-2.
J Med Virol, 95:e29163-e29163, 2023

PubMed Abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2). While evolutionarily conserved, ACE2 receptors differ across various species and differential interactions with Spike (S) glycoproteins of SARS-CoV-2 viruses impact species specificity. Reverse zoonoses led to SARS-CoV-2 outbreaks on multiple American mink (Mustela vison) farms during the pandemic and gave rise to mink-associated S substitutions known for transmissibility between mink and zoonotic transmission to humans. In this study, we used bio-layer interferometry (BLI) to discern the differences in binding affinity between multiple human and mink-derived S glycoproteins of SARS-CoV-2 and their respective ACE2 receptors. Further, we conducted a structural analysis of a mink variant S glycoprotein and American mink ACE2 (mvACE2) using cryo-electron microscopy (cryo-EM), revealing four distinct conformations. We discovered a novel intermediary conformation where the mvACE2 receptor is bound to the receptor-binding domain (RBD) of the S glycoprotein in a "down" position, approximately 34° lower than previously reported "up" RBD. Finally, we compared residue interactions in the S-ACE2 complex interface of S glycoprotein conformations with varying RBD orientations. These findings provide valuable insights into the molecular mechanisms of SARS-CoV-2 entry.

PubMed: 37842796
DOI: 10.1002/jmv.29163

実験手法

ELECTRON MICROSCOPY (3.83 Å)