1. Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles.
- Author
-
Lu M, Uchil PD, Li W, Zheng D, Terry DS, Gorman J, Shi W, Zhang B, Zhou T, Ding S, Gasser R, Prévost J, Beaudoin-Bussières G, Anand SP, Laumaea A, Grover JR, Liu L, Ho DD, Mascola JR, Finzi A, Kwong PD, Blanchard SC, and Mothes W
- Subjects
- Antibodies, Monoclonal immunology, Antibodies, Viral immunology, COVID-19 immunology, COVID-19 pathology, COVID-19 virology, Epitopes immunology, Humans, Membrane Glycoproteins genetics, Membrane Glycoproteins ultrastructure, Protein Binding immunology, Receptors, Virus genetics, Receptors, Virus immunology, Receptors, Virus ultrastructure, SARS-CoV-2 genetics, SARS-CoV-2 pathogenicity, Spike Glycoprotein, Coronavirus genetics, Spike Glycoprotein, Coronavirus immunology, Virion genetics, Virion ultrastructure, Virus Internalization, COVID-19 genetics, Protein Conformation, SARS-CoV-2 ultrastructure, Spike Glycoprotein, Coronavirus ultrastructure
- Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) mediates viral entry into cells and is critical for vaccine development against coronavirus disease 2019 (COVID-19). Structural studies have revealed distinct conformations of S, but real-time information that connects these structures is lacking. Here we apply single-molecule fluorescence (Förster) resonance energy transfer (smFRET) imaging to observe conformational dynamics of S on virus particles. Virus-associated S dynamically samples at least four distinct conformational states. In response to human receptor angiotensin-converting enzyme 2 (hACE2), S opens sequentially into the hACE2-bound S conformation through at least one on-path intermediate. Conformational preferences observed upon exposure to convalescent plasma or antibodies suggest mechanisms of neutralization involving either competition with hACE2 for binding to the receptor-binding domain (RBD) or allosteric interference with conformational changes required for entry. Our findings inform on mechanisms of S recognition and conformations for immunogen design., Competing Interests: Declaration of Interests S.C.B. has an equity interest in Lumidyne Technologies., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF