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dc.contributor.authorSantamaria, Andreas
dc.contributor.authorBatchu, Krishna C
dc.contributor.authorMatsarskaia, Olga
dc.contributor.authorPrévost, Sylvain F
dc.contributor.authorRusso, Daniela
dc.contributor.authorNatali, Francesca
dc.contributor.authorSeydel, Tilo
dc.contributor.authorHoffmann, Ingo
dc.contributor.authorLaux, Valérie
dc.contributor.authorHaertlein, Michael
dc.contributor.authorDarwish, Tamim A
dc.contributor.authorRussell, Robert A
dc.contributor.authorCorucci, Giacomo
dc.contributor.authorFragneto, Giovanna
dc.contributor.authorMaestro, Armando
dc.contributor.authorZaccai, Nathan
dc.date.accessioned2022-03-19T02:06:24Z
dc.date.available2022-03-19T02:06:24Z
dc.date.issued2022-02-23
dc.identifier.issn0002-7863
dc.identifier.other35157798
dc.identifier.otherPMC8862744
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/335206
dc.descriptionFunder: National Collaborative Research Infrastructure Strategy (NCRIS)
dc.descriptionFunder: ANR/NSF-PIRE
dc.descriptionFunder: Science and Technology Facilities Council
dc.descriptionFunder: Institut Laue Langevin
dc.description.abstractCoronavirus disease-2019 (COVID-19), a potentially lethal respiratory illness caused by the coronavirus SARS-CoV-2, emerged in the end of 2019 and has since spread aggressively across the globe. A thorough understanding of the molecular mechanisms of cellular infection by coronaviruses is therefore of utmost importance. A critical stage in infection is the fusion between viral and host membranes. Here, we present a detailed investigation of the role of selected SARS-CoV-2 Spike fusion peptides, and the influence of calcium and cholesterol, in this fusion process. Structural information from specular neutron reflectometry and small angle neutron scattering, complemented by dynamics information from quasi-elastic and spin-echo neutron spectroscopy, revealed strikingly different functions encoded in the Spike fusion domain. Calcium drives the N-terminal of the Spike fusion domain to fully cross the host plasma membrane. Removing calcium, however, reorients the peptide back to the lipid leaflet closest to the virus, leading to significant changes in lipid fluidity and rigidity. In conjunction with other regions of the fusion domain, which are also positioned to bridge and dehydrate viral and host membranes, the molecular events leading to cell entry by SARS-CoV-2 are proposed.
dc.languageeng
dc.publisherAmerican Chemical Society (ACS)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceessn: 1520-5126
dc.sourcenlmid: 7503056
dc.subjectCholesterol
dc.subjectLipid Bilayers
dc.subjectPeptide Fragments
dc.subjectNeutron Diffraction
dc.subjectMembrane Fluidity
dc.subjectAmino Acid Sequence
dc.subjectScattering, Small Angle
dc.subjectUnilamellar Liposomes
dc.subjectSpike Glycoprotein, Coronavirus
dc.subjectProtein Domains
dc.subjectSARS-CoV-2
dc.titleStrikingly Different Roles of SARS-CoV-2 Fusion Peptides Uncovered by Neutron Scattering.
dc.typeArticle
dc.date.updated2022-03-19T02:06:24Z
prism.endingPage2979
prism.issueIdentifier7
prism.publicationNameJ Am Chem Soc
prism.startingPage2968
prism.volume144
dc.identifier.doi10.17863/CAM.82636
dcterms.dateAccepted2021-12-24
rioxxterms.versionofrecord10.1021/jacs.1c09856
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.contributor.orcidSantamaria, Andreas [0000-0002-6151-4406]
dc.contributor.orcidMatsarskaia, Olga [0000-0002-7293-7287]
dc.contributor.orcidSeydel, Tilo [0000-0001-9630-1630]
dc.contributor.orcidHoffmann, Ingo [0000-0001-7178-6467]
dc.contributor.orcidDarwish, Tamim A [0000-0001-7704-1837]
dc.contributor.orcidMaestro, Armando [0000-0002-7791-8130]
dc.contributor.orcidZaccai, Nathan [0000-0002-1476-2044]
dc.identifier.eissn1520-5126
pubs.funder-project-idWellcome Trust (090909/Z/09/Z)
pubs.funder-project-idWellcome Trust (207455/Z/17/Z)
cam.issuedOnline2022-02-14


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International