7SY2

Cryo-EM structure of the SARS-CoV-2 D614G,N501Y mutant spike protein ectodomain bound to human ACE2 ectodomain (focused refinement of RBD and ACE2)

7SY2 の概要

• エントリーDOI: 10.2210/pdb7sy2/pdb
• EMDBエントリー: 25514
• 分子名称: Spike glycoprotein, Processed angiotensin-converting enzyme 2, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: sars-cov-2, glycoprotein, fusion protein, viral protein, ace2, viral protein-hydrolase complex, viral protein/hydrolase
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 214353.92

構造登録者

Zhu, X.,Mannar, D.,Saville, J.W.,Srivastava, S.S.,Berezuk, A.M.,Zhou, S.,Tuttle, K.S.,Kim, A.,Li, W.,Dimitrov, D.S.,Subramaniam, S. (登録日: 2021-11-24, 公開日: 2021-12-29, 最終更新日: 2024-10-23)

主引用文献

Mannar, D.,Saville, J.W.,Zhu, X.,Srivastava, S.S.,Berezuk, A.M.,Zhou, S.,Tuttle, K.S.,Kim, A.,Li, W.,Dimitrov, D.S.,Subramaniam, S.
Structural analysis of receptor binding domain mutations in SARS-CoV-2 variants of concern that modulate ACE2 and antibody binding.
Cell Rep, 37:110156-110156, 2021

PubMed Abstract: The recently emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Beta (B.1.351) and Gamma (P.1) variants of concern (VoCs) include a key mutation (N501Y) found in the Alpha (B.1.1.7) variant that enhances affinity of the spike protein for its receptor, angiotensin-converting enzyme 2 (ACE2). Additional mutations are found in these variants at residues 417 and 484 that appear to promote antibody evasion. In contrast, the Epsilon variants (B.1.427/429) lack the N501Y mutation yet exhibit antibody evasion. We have engineered spike proteins to express these receptor binding domain (RBD) VoC mutations either in isolation or in different combinations and analyze the effects using biochemical assays and cryoelectron microscopy (cryo-EM) structural analyses. Overall, our findings suggest that the emergence of new SARS-CoV-2 variant spikes can be rationalized as the result of mutations that confer increased ACE2 affinity, increased antibody evasion, or both, providing a framework to dissect the molecular factors that drive VoC evolution.

PubMed: 34914928
DOI: 10.1016/j.celrep.2021.110156

実験手法

ELECTRON MICROSCOPY (3.11 Å)