Strikingly Different Roles of SARS-CoV-2 Fusion Peptides Uncovered by Neutron Scattering.
View / Open Files
Authors
Batchu, Krishna C
Prévost, Sylvain F
Russo, Daniela
Natali, Francesca
Laux, Valérie
Haertlein, Michael
Russell, Robert A
Corucci, Giacomo
Fragneto, Giovanna
Publication Date
2022-02-23Journal Title
J Am Chem Soc
ISSN
0002-7863
Publisher
American Chemical Society (ACS)
Volume
144
Issue
7
Pages
2968-2979
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Santamaria, A., Batchu, K. C., Matsarskaia, O., Prévost, S. F., Russo, D., Natali, F., Seydel, T., et al. (2022). Strikingly Different Roles of SARS-CoV-2 Fusion Peptides Uncovered by Neutron Scattering.. J Am Chem Soc, 144 (7), 2968-2979. https://doi.org/10.1021/jacs.1c09856
Description
Funder: National Collaborative Research Infrastructure Strategy (NCRIS)
Funder: ANR/NSF-PIRE
Funder: Science and Technology Facilities Council
Funder: Institut Laue Langevin
Abstract
Coronavirus 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.
Keywords
Cholesterol, Lipid Bilayers, Peptide Fragments, Neutron Diffraction, Membrane Fluidity, Amino Acid Sequence, Scattering, Small Angle, Unilamellar Liposomes, Spike Glycoprotein, Coronavirus, Protein Domains, SARS-CoV-2
Sponsorship
Wellcome Trust (090909/Z/09/Z)
Wellcome Trust (207455/Z/17/Z)
Identifiers
35157798, PMC8862744
External DOI: https://doi.org/10.1021/jacs.1c09856
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335206
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.