Department of Microbiology and Physiological Systems; MassBiologics; Program in Molecular Medicine; Department of Biochemistry and Molecular Biotechnology
Amino Acids, Peptides, and Proteins | Biophysics | Immunology and Infectious Disease | Infectious Disease | Structural Biology | Virology | Virus Diseases
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells through binding to angiotensin-converting enzyme 2 (ACE2). This interaction is mediated by the receptor-binding domain (RBD) of the viral spike (S) glycoprotein. Structural and dynamic data have shown that S can adopt multiple conformations, which controls the exposure of the ACE2-binding site in the RBD. Here, using single-molecule Forster resonance energy transfer (smFRET) imaging, we report the effects of ACE2 and antibody binding on the conformational dynamics of S from the Wuhan-1 strain and in the presence of the D614G mutation. We find that D614G modulates the energetics of the RBD position in a manner similar to ACE2 binding. We also find that antibodies that target diverse epitopes, including those distal to the RBD, stabilize the RBD in a position competent for ACE2 binding. Parallel solution-based binding experiments using fluorescence correlation spectroscopy (FCS) indicate antibody-mediated enhancement of ACE2 binding. These findings inform on novel strategies for therapeutic antibody cocktails.
infectious disease, microbiology, molecular biophysics, protein dynamics, single-molecule biophysics, structural biology, virus entry, viruses
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Copyright © 2022, Díaz-Salinas et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
DOI of Published Version
Díaz-Salinas MA, Li Q, Ejemel M, Yurkovetskiy L, Luban J, Shen K, Wang Y, Munro JB. Conformational dynamics and allosteric modulation of the SARS-CoV-2 spike. Elife. 2022 Mar 24;11:e75433. doi: 10.7554/eLife.75433. PMID: 35323111; PMCID: PMC8963877. Link to article on publisher's site
Diaz-Salinas MA, Li Q, Monir E, Yurkovetskiy L, Luban J, Shen K, Wang Y, Munro JB. (2022). Conformational dynamics and allosteric modulation of the SARS-CoV-2 spike. COVID-19 Publications by UMass Chan Authors. https://doi.org/10.7554/eLife.75433. Retrieved from https://escholarship.umassmed.edu/covid19/368
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