7EDH

Cryo-EM structure of SARS-CoV-2 S-UK variant (B.1.1.7), one RBD-up conformation 3

Summary for 7EDH

• Entry DOI: 10.2210/pdb7edh/pdb
• Related: 7EDF 7EDG
• EMDB information: 31069 31070 31071
• Descriptor: Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: sars-cov-2, spike protein, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2)
• Total number of polymer chains: 3
• Total formula weight: 444421.89

Authors

Yang, T.J.,Yu, P.Y.,Chang, Y.C.,Wu, H.C.,Hsu, S.T.D. (deposition date: 2021-03-16, release date: 2021-09-01, Last modification date: 2024-11-20)

Primary citation

Yang, T.J.,Yu, P.Y.,Chang, Y.C.,Liang, K.H.,Tso, H.C.,Ho, M.R.,Chen, W.Y.,Lin, H.T.,Wu, H.C.,Hsu, S.D.
Effect of SARS-CoV-2 B.1.1.7 mutations on spike protein structure and function.
Nat.Struct.Mol.Biol., 28:731-739, 2021

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) 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.

PubMed: 34385690
DOI: 10.1038/s41594-021-00652-z

Experimental method

ELECTRON MICROSCOPY (3.6 Å)