EMD-31071
Cryo-EM structure of SARS-CoV-2 S-UK variant (B.1.1.7), one RBD-up conformation 3
EMD-31071
Single-particle3.6 Å

Map released: 01/09/2021
Last modified: 20/11/2024
Sample Organism:
Severe acute respiratory syndrome coronavirus 2
Sample: SARS-CoV-2 spike glycoprotein
Fitted models: 7edh (Avg. Q-score: 0.415)
Deposition Authors: Yang TJ
,
Yu PY
Sample: SARS-CoV-2 spike glycoprotein
Fitted models: 7edh (Avg. Q-score: 0.415)
Deposition Authors: Yang TJ


Effect of SARS-CoV-2 B.1.1.7 mutations on spike protein structure and function.
Yang TJ
,
Yu PY
,
Chang YC
,
Liang KH
,
Tso HC,
Ho MR
,
Chen WY,
Lin HT,
Wu HC
,
Hsu SD
(2021) Nat Struct Mol Biol , 28 , 731 - 739







(2021) Nat Struct Mol Biol , 28 , 731 - 739
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.
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.