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.
🔬 Techniques
💻 Software
✨ Fluorophores
🧪 Sample Preparation
🏭 Microscope Brands
💻 Software Details
💾 Data Repositories
🏛️ Research Organizations (ROR)
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📊 Figures
Fig. 1
Characterization of the purified full-length SARS-CoV-2 S proteins.
( A ) The full-length SARS-CoV-2 S protein carrying either D614 or G614 was extracted and purified in detergent n-dodecyl-- d -maltopyranoside (DDM) and further resolved by gel-filtration chromatograp...
Fig. 2
Cryo-EM structures of the full-length SARS-CoV-2 S protein carrying G614.
( A ) Three structures of the G614 S trimerrepresenting a closed, three RBDdown conformation; an RBD-intermediate conformation; and a one RBDup conformationwere modeled on the basis of corresponding c...
Fig. 3
Cryo-EM structures of the full-length SARS-CoV-2 S protein carrying G614.
( A ) (Top) The structure of the closed, three RBDdown conformation of the D614 S trimer is shown in ribbon diagram with one protomer colored as NTD in blue, RBD in cyan, CTD1 in green, CTD2 in light ...
Fig. 4
Close-up views of the D614G substitution.
( A ) A close-up view of the region near the residue 614 with superposition of the G614 trimer structure in green (CTD2) and magenta (FPPR) and the D614 trimer in yellow, both in the closed prefusion ...
Figure images are served from the NIH/NLM PubMed Central Open Access Subset or Europe PMC; copyright remains with the publishers and authors.
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