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Title | Effect of SARS-CoV-2 B.1.1.7 mutations on spike protein structure and function. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 28, Issue 9, Page 731-739, Year 2021 |
Publish date | Aug 12, 2021 |
Authors | Tzu-Jing Yang / Pei-Yu Yu / Yuan-Chih Chang / Kang-Hao Liang / Hsian-Cheng Tso / Meng-Ru Ho / Wan-Yu Chen / Hsiu-Ting Lin / Han-Chung Wu / Shang-Te Danny Hsu / |
PubMed Abstract | The B.1.1.7 variant of SARS-CoV-2 first detected in the UK harbors amino-acid substitutions and deletions in the spike protein that potentially enhance host angiotensin conversion enzyme 2 (ACE2) ...The B.1.1.7 variant of SARS-CoV-2 first detected in the UK harbors amino-acid substitutions and deletions in the spike protein that potentially enhance host angiotensin conversion enzyme 2 (ACE2) receptor binding and viral immune evasion. Here we report cryo-EM structures of the spike protein of B.1.1.7 in the apo and ACE2-bound forms. The apo form showed one or two receptor-binding domains (RBDs) in the open conformation, without populating the fully closed state. All three RBDs were engaged in ACE2 binding. The B.1.1.7-specific A570D mutation introduces a molecular switch that could modulate the opening and closing of the RBD. The N501Y mutation introduces a π-π interaction that enhances RBD binding to ACE2 and abolishes binding of a potent neutralizing antibody (nAb). Cryo-EM also revealed how a cocktail of two nAbs simultaneously bind to all three RBDs, and demonstrated the potency of the nAb cocktail to neutralize different SARS-CoV-2 pseudovirus strains, including B.1.1.7. |
External links | Nat Struct Mol Biol / PubMed:34385690 |
Methods | EM (single particle) |
Resolution | 3.2 - 4.03 Å |
Structure data | EMDB-31069, PDB-7edf: EMDB-31070, PDB-7edg: EMDB-31071, PDB-7edh: EMDB-31072, PDB-7edi: EMDB-31073, PDB-7edj: EMDB-31074: Cryo-EM structure of SARS-CoV-2 S-D614G variant in complex with neutralizing antibodies, RBD-chAb-15 and RBD-chAb45 |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN / SARS-CoV-2 / Spike protein / Neutralizing antibody |