biostudies-literatureDiaz-Salinas MAUMass Chan Medical School COVID-19 Pandemic Relief FundNIAID NIH HHSEvergrande COVID-19 Response FundNCI NIH HHSMassachusetts Consortium on Pathogen ReadinessNational Institutes of HealthNIH HHSWorcester Foundation for Biomedical Researche75433https://www.ebi.ac.uk/biostudies/studies/S-EPMC8963877biostudies-literatureUnknown11Severe 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 Förster 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 teLifeConformational dynamics and allosteric modulation of the SARS-CoV-2 spike.PMC8963877K22 CA241362R37 AI047868K22CA241362R37AI147868R37 AI147868R01AI148784R01 AI148784Yurkovetskiy LShen KDiaz-Salinas MALuban JMunro JBLi QWang YEjemel MfalseConformational dynamics and allosteric modulation of the SARS-CoV-2 spike.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 Förster 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 t2022-01-01T00:00:00Z2022 Mar2026-05-31T06:00:59.06Z2025-02-19T01:54:34.735ZS-EPMC89638773532311110.7554/eLife.75433