Dhiraj Mannar / James W Saville / Xing Zhu / Shanti S Srivastava / Alison M Berezuk / Steven Zhou / Katharine S Tuttle / Andrew Kim / Wei Li / Dimiter S Dimitrov / Sriram Subramaniam /
PubMed 要旨
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) ...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.
EMDB-25509, PDB-7sxx: Cryo-EM structure of the SARS-CoV-2 D614G mutant spike protein ectodomain bound to human ACE2 ectodomain (global refinement) 手法: EM (単粒子) / 解像度: 2.66 Å
EMDB-25510, PDB-7sxy: Cryo-EM structure of the SARS-CoV-2 D614G mutant spike protein ectodomain bound to human ACE2 ectodomain (focused refinement of RBD and ACE2) 手法: EM (単粒子) / 解像度: 2.79 Å
EMDB-25511, PDB-7sxz: Cryo-EM structure of the SARS-CoV-2 D614G,L452R mutant spike protein ectodomain bound to human ACE2 ectodomain (global refinement) 手法: EM (単粒子) / 解像度: 2.61 Å
EMDB-25512, PDB-7sy0: Cryo-EM structure of the SARS-CoV-2 D614G,L452R mutant spike protein ectodomain bound to human ACE2 ectodomain (focused refinement of RBD and ACE2) 手法: EM (単粒子) / 解像度: 3.0 Å
EMDB-25513, PDB-7sy1: Cryo-EM structure of the SARS-CoV-2 D614G,N501Y mutant spike protein ectodomain bound to human ACE2 ectodomain (global refinement) 手法: EM (単粒子) / 解像度: 2.83 Å
EMDB-25514, PDB-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) 手法: EM (単粒子) / 解像度: 3.11 Å
EMDB-25515, PDB-7sy3: Cryo-EM structure of the SARS-CoV-2 D614G,N501Y,E484K mutant spike protein ectodomain bound to human ACE2 ectodomain (global refinement) 手法: EM (単粒子) / 解像度: 2.95 Å
EMDB-25516, PDB-7sy4: Cryo-EM structure of the SARS-CoV-2 D614G,N501Y,E484K mutant spike protein ectodomain bound to human ACE2 ectodomain (focused refinement of RBD and ACE2) 手法: EM (単粒子) / 解像度: 3.35 Å
EMDB-25517, PDB-7sy5: Cryo-EM structure of the SARS-CoV-2 D614G,N501Y,E484K,K417N mutant spike protein ectodomain bound to human ACE2 ectodomain (global refinement) 手法: EM (単粒子) / 解像度: 2.59 Å
EMDB-25518, PDB-7sy6: Cryo-EM structure of the SARS-CoV-2 D614G,N501Y,E484K,K417N mutant spike protein ectodomain bound to human ACE2 ectodomain (focused refinement of RBD and ACE2) 手法: EM (単粒子) / 解像度: 2.81 Å
EMDB-25519, PDB-7sy7: Cryo-EM structure of the SARS-CoV-2 D614G,N501Y,E484K,K417T mutant spike protein ectodomain bound to human ACE2 ectodomain (global refinement) 手法: EM (単粒子) / 解像度: 2.81 Å
EMDB-25520, PDB-7sy8: Cryo-EM structure of the SARS-CoV-2 D614G,N501Y,E484K,K417T mutant spike protein ectodomain bound to human ACE2 ectodomain (focused refinement of RBD and ACE2) 手法: EM (単粒子) / 解像度: 3.14 Å