7LWN

Mink Cluster 5-associated SARS-CoV-2 spike protein (S-GSAS-D614G-delFV) in the 1-RBD up conformation

Summary for 7LWN

• Entry DOI: 10.2210/pdb7lwn/pdb
• EMDB information: 23551
• Descriptor: Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: sars-cov-2 spike protein trimer, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2)
• Total number of polymer chains: 3
• Total formula weight: 434419.00

Authors

Gobeil, S.,Acharya, P. (deposition date: 2021-03-01, release date: 2021-03-31, Last modification date: 2024-10-23)

Primary citation

Gobeil, S.M.,Janowska, K.,McDowell, S.,Mansouri, K.,Parks, R.,Stalls, V.,Kopp, M.F.,Manne, K.,Li, D.,Wiehe, K.,Saunders, K.O.,Edwards, R.J.,Korber, B.,Haynes, B.F.,Henderson, R.,Acharya, P.
Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity.
Science, 373:-, 2021

PubMed Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike mutations enable increased transmission and antibody resistance. We combined cryo-electron microscopy (cryo-EM), binding, and computational analyses to study variant spikes, including one that was involved in transmission between minks and humans, and others that originated and spread in human populations. All variants showed increased angiotensin-converting enzyme 2 (ACE2) receptor binding and increased propensity for receptor binding domain (RBD)-up states. While adaptation to mink resulted in spike destabilization, the B.1.1.7 (UK) spike balanced stabilizing and destabilizing mutations. A local destabilizing effect of the RBD E484K mutation was implicated in resistance of the B.1.1.28/P.1 (Brazil) and B.1.351 (South Africa) variants to neutralizing antibodies. Our studies revealed allosteric effects of mutations and mechanistic differences that drive either interspecies transmission or escape from antibody neutralization.

PubMed: 34168071
DOI: 10.1126/science.abi6226

Experimental method

ELECTRON MICROSCOPY (2.94 Å)