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dc.contributor.authorDiaz-Salinas, Marco A.
dc.contributor.authorLi, Qi
dc.contributor.authorMonir, Ejemel
dc.contributor.authorYurkovetskiy, Leonid
dc.contributor.authorLuban, Jeremy
dc.contributor.authorShen, Kuang
dc.contributor.authorWang, Yang
dc.contributor.authorMunro, James B.
dc.date2022-08-11T08:08:11.000
dc.date.accessioned2022-08-23T15:45:36Z
dc.date.available2022-08-23T15:45:36Z
dc.date.issued2022-03-24
dc.date.submitted2022-03-31
dc.identifier.citation<p>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. <a href="https://doi.org/10.7554/eLife.75433">Link to article on publisher's site</a></p>
dc.identifier.issn2050-084X (Linking)
dc.identifier.doi10.7554/eLife.75433
dc.identifier.pmid35323111
dc.identifier.urihttp://hdl.handle.net/20.500.14038/27567
dc.description.abstractSevere 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=35323111&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 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.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectinfectious disease
dc.subjectmicrobiology
dc.subjectmolecular biophysics
dc.subjectprotein dynamics
dc.subjectsingle-molecule biophysics
dc.subjectstructural biology
dc.subjectvirus entry
dc.subjectviruses
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiophysics
dc.subjectImmunology and Infectious Disease
dc.subjectInfectious Disease
dc.subjectStructural Biology
dc.subjectVirology
dc.subjectVirus Diseases
dc.titleConformational dynamics and allosteric modulation of the SARS-CoV-2 spike
dc.typeArticle
dc.source.journaltitleeLife
dc.source.volume11
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1376&amp;context=covid19&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/covid19/368
dc.identifier.contextkey28457063
refterms.dateFOA2022-08-23T15:45:36Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathcovid19/368
dc.contributor.departmentDepartment of Biochemistry and Molecular Biotechnology
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentMassBiologics
dc.contributor.departmentDepartment of Microbiology and Physiological Systems
dc.source.pagese75433


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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.
Except where otherwise noted, this item's license is described as 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.