7MJM

Cryo-EM structure of the SARS-CoV-2 N501Y mutant spike protein ectodomain bound to human ACE2 ectodomain

Summary for 7MJM

• Entry DOI: 10.2210/pdb7mjm/pdb
• EMDB information: 23878
• Descriptor: Spike glycoprotein, Processed angiotensin-converting enzyme 2, 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, glycoprotein, fusion protein, viral protein, ace2
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 5
• Total formula weight: 582921.36

Authors

Zhu, X.,Mannar, D.,Srivastava, S.S.,Berezuk, A.M.,Demers, J.P.,Saville, J.W.,Leopold, K.,Li, W.,Dimitrov, D.S.,Tuttle, K.S.,Zhou, S.,Chittori, S.,Subramaniam, S. (deposition date: 2021-04-20, release date: 2021-05-12, Last modification date: 2024-10-16)

Primary citation

Zhu, X.,Mannar, D.,Srivastava, S.S.,Berezuk, A.M.,Demers, J.P.,Saville, J.W.,Leopold, K.,Li, W.,Dimitrov, D.S.,Tuttle, K.S.,Zhou, S.,Chittori, S.,Subramaniam, S.
Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies.
Plos Biol., 19:e3001237-e3001237, 2021

PubMed Abstract: The recently reported "UK variant" (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result of several changes, including the N501Y mutation. We present a 2.9-Å resolution cryo-electron microscopy (cryo-EM) structure of the complex between the ACE2 receptor and N501Y spike protein ectodomains that shows Y501 inserted into a cavity at the binding interface near Y41 of ACE2. This additional interaction provides a structural explanation for the increased ACE2 affinity of the N501Y mutant, and likely contributes to its increased infectivity. However, this mutation does not result in large structural changes, enabling important neutralization epitopes to be retained in the spike receptor binding domain. We confirmed this through biophysical assays and by determining cryo-EM structures of spike protein ectodomains bound to 2 representative potent neutralizing antibody fragments.

PubMed: 33914735
DOI: 10.1371/journal.pbio.3001237

Experimental method

ELECTRON MICROSCOPY (2.83 Å)