Cargando…

Progressive membrane-binding mechanism of SARS-CoV-2 variant spike proteins

Membrane recognition by viral spike proteins is critical for infection. Here we show the host cell membrane-binding surfaces of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike variants Alpha, Beta, Gamma, Delta, Epsilon, Kappa, and Omicron as well as SARS-CoV-1 and pangolin and ba...

Descripción completa

Detalles Bibliográficos
Autores principales: Overduin, Michael, Kervin, Troy A., Tran, Anh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251956/
https://www.ncbi.nlm.nih.gov/pubmed/35813872
http://dx.doi.org/10.1016/j.isci.2022.104722
_version_ 1784740150906978304
author Overduin, Michael
Kervin, Troy A.
Tran, Anh
author_facet Overduin, Michael
Kervin, Troy A.
Tran, Anh
author_sort Overduin, Michael
collection PubMed
description Membrane recognition by viral spike proteins is critical for infection. Here we show the host cell membrane-binding surfaces of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike variants Alpha, Beta, Gamma, Delta, Epsilon, Kappa, and Omicron as well as SARS-CoV-1 and pangolin and bat relatives. They show increases in membrane binding propensities over time, with all spike head mutations in variants, and particularly BA.1, impacting the protein’s affinity to cell membranes. Comparison of hundreds of structures yields a progressive model of membrane docking in which spike protein trimers shift from initial perpendicular stances to increasingly tilted positions that draw viral particles alongside host cell membranes before optionally engaging angiotensin-converting enzyme 2 (ACE2) receptors. This culminates in the assembly of the symmetric fusion apparatus, with enhanced membrane interactions of variants explaining their unique cell fusion capacities and COVID-19 disease transmission rates.
format Online
Article
Text
id pubmed-9251956
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-92519562022-07-05 Progressive membrane-binding mechanism of SARS-CoV-2 variant spike proteins Overduin, Michael Kervin, Troy A. Tran, Anh iScience Article Membrane recognition by viral spike proteins is critical for infection. Here we show the host cell membrane-binding surfaces of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike variants Alpha, Beta, Gamma, Delta, Epsilon, Kappa, and Omicron as well as SARS-CoV-1 and pangolin and bat relatives. They show increases in membrane binding propensities over time, with all spike head mutations in variants, and particularly BA.1, impacting the protein’s affinity to cell membranes. Comparison of hundreds of structures yields a progressive model of membrane docking in which spike protein trimers shift from initial perpendicular stances to increasingly tilted positions that draw viral particles alongside host cell membranes before optionally engaging angiotensin-converting enzyme 2 (ACE2) receptors. This culminates in the assembly of the symmetric fusion apparatus, with enhanced membrane interactions of variants explaining their unique cell fusion capacities and COVID-19 disease transmission rates. Elsevier 2022-07-04 /pmc/articles/PMC9251956/ /pubmed/35813872 http://dx.doi.org/10.1016/j.isci.2022.104722 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Overduin, Michael
Kervin, Troy A.
Tran, Anh
Progressive membrane-binding mechanism of SARS-CoV-2 variant spike proteins
title Progressive membrane-binding mechanism of SARS-CoV-2 variant spike proteins
title_full Progressive membrane-binding mechanism of SARS-CoV-2 variant spike proteins
title_fullStr Progressive membrane-binding mechanism of SARS-CoV-2 variant spike proteins
title_full_unstemmed Progressive membrane-binding mechanism of SARS-CoV-2 variant spike proteins
title_short Progressive membrane-binding mechanism of SARS-CoV-2 variant spike proteins
title_sort progressive membrane-binding mechanism of sars-cov-2 variant spike proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251956/
https://www.ncbi.nlm.nih.gov/pubmed/35813872
http://dx.doi.org/10.1016/j.isci.2022.104722
work_keys_str_mv AT overduinmichael progressivemembranebindingmechanismofsarscov2variantspikeproteins
AT kervintroya progressivemembranebindingmechanismofsarscov2variantspikeproteins
AT trananh progressivemembranebindingmechanismofsarscov2variantspikeproteins