Strikingly different roles of SARS-CoV‑2 fusion peptides uncovered by neutron scattering

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dc.contributor.authorSantamaria, Aen_AU
dc.contributor.authorBatchu, KCen_AU
dc.contributor.authorMatsarskaia, Oen_AU
dc.contributor.authorPrévost, SFen_AU
dc.contributor.authorRusso, Den_AU
dc.contributor.authorNatali, Fen_AU
dc.contributor.authorSeydel, Ten_AU
dc.contributor.authorHoffmann, Ien_AU
dc.contributor.authorLaux, Ven_AU
dc.contributor.authorHaertlein, Men_AU
dc.contributor.authorDarwish, TAen_AU
dc.contributor.authorRussell, RAen_AU
dc.contributor.authorCorucci, Gen_AU
dc.contributor.authorFragneto, Gen_AU
dc.contributor.authorMaestro, Aen_AU
dc.contributor.authorZaccai, NRen_AU
dc.date.accessioned2024-02-23T02:08:03Zen_AU
dc.date.available2024-02-23T02:08:03Zen_AU
dc.date.issued2022-02-14en_AU
dc.date.statistics2024-02-23en_AU
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. © 2022 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY-NC-ND 4.0.en_AU
dc.description.sponsorshipThe authors thank the ILL for awarding beam-time: SNR and SANS (DOI: 10.5291/ILL-DATA.DIR-215), and QENS and NSE (DOI: 10.5291/ILL-DATA.DIR-211), and use of support facilities at the D-Lab and Partnership for Soft Condensed Matter (PSCM). Financial support for consumables was also provided by the Science and Technology Facilities Council (U.K.). N.R.Z. was supported by Wellcome Trust grant WT 207455/Z/17/Z. Part of the lipid extraction activity was funded by the ANR/NSF-PIRE project REACT (Research and Education in Active Coatings Technologies for Human Health). The National Deuteration Facility in Australia is partly funded by The National Collaborative Research Infrastructure Strategy (NCRIS), an Australian Government initiative. We gratefully acknowledge M. Jourdan and J. Dejeu (Université Grenoble Alpes) for access to the CD instrument; J. Carrascosa-Tejedor for help in the analysis of the SNR data collected; and Prof. E. Guzman, Prof. P. Luzio, Prof. D. Owen, and Dr. J. Zaccai for a critical reading of this manuscript. We would also like to thank S. Monfront for the cover art.en_AU
dc.format.mediumPrint-Electronicen_AU
dc.identifier.citationSantamaria, A., Batchu, K. C., Matsarskaia, O., Prévost, S. F., Russo, D., Natali, F., Seydel, I., Hoffman, I., Laux, V., Haertein, M., Darwish, T. A., Russell, R. A., Corucci, G., Fragneto, G., Maestro, A., & Zaccai, N. R. (2022). Strikingly different roles of SARS-CoV-2 fusion peptides uncovered by neutron scattering. Journal of the American Chemical Society, 144(7), 2968-2979. doi:10.1021/jacs.1c09856en_AU
dc.identifier.issn0002-7863en_AU
dc.identifier.issn1520-5126en_AU
dc.identifier.issue7en_AU
dc.identifier.journaltitleJournal of the American Chemical Societyen_AU
dc.identifier.pagination2968-2979en_AU
dc.identifier.urihttp://dx.doi.org/10.1021/jacs.1c09856en_AU
dc.identifier.urihttps://apo.ansto.gov.au/handle/10238/15416en_AU
dc.identifier.volume144en_AU
dc.languageEnglishen_AU
dc.language.isoenen_AU
dc.publisherAmerican Chemical Society (ACS)en_AU
dc.subjectCoronavirusesen_AU
dc.subjectPeptidesen_AU
dc.subjectNeutron diffractionen_AU
dc.subjectViral diseasesen_AU
dc.subjectrespiratory system diseasesen_AU
dc.subjectInfectious diseasesen_AU
dc.subjectMembranesen_AU
dc.subjectSmall angle scatteringen_AU
dc.titleStrikingly different roles of SARS-CoV‑2 fusion peptides uncovered by neutron scatteringen_AU
dc.typeJournal Articleen_AU
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