Structural dynamics in the evolution of SARS-CoV-2 spike glycoprotein

Valeria Calvaresi (), Antoni G. Wrobel (), Joanna Toporowska, Dietmar Hammerschmid, Katie J. Doores, Richard T. Bradshaw, Ricardo B. Parsons, Donald J. Benton, Chloë Roustan, Eamonn Reading, Michael H. Malim, Steve J. Gamblin and Argyris Politis ()
Additional contact information
Valeria Calvaresi: King’s College London
Antoni G. Wrobel: The Francis Crick Institute
Joanna Toporowska: King’s College London
Dietmar Hammerschmid: King’s College London
Katie J. Doores: School of Immunology and Microbial Sciences, King’s College London
Richard T. Bradshaw: King’s College London
Ricardo B. Parsons: King’s College London
Donald J. Benton: The Francis Crick Institute
Chloë Roustan: The Francis Crick Institute
Eamonn Reading: King’s College London
Michael H. Malim: School of Immunology and Microbial Sciences, King’s College London
Steve J. Gamblin: The Francis Crick Institute
Argyris Politis: King’s College London

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract SARS-CoV-2 spike glycoprotein mediates receptor binding and subsequent membrane fusion. It exists in a range of conformations, including a closed state unable to bind the ACE2 receptor, and an open state that does so but displays more exposed antigenic surface. Spikes of variants of concern (VOCs) acquired amino acid changes linked to increased virulence and immune evasion. Here, using HDX-MS, we identified changes in spike dynamics that we associate with the transition from closed to open conformations, to ACE2 binding, and to specific mutations in VOCs. We show that the RBD-associated subdomain plays a role in spike opening, whereas the NTD acts as a hotspot of conformational divergence of VOC spikes driving immune evasion. Alpha, beta and delta spikes assume predominantly open conformations and ACE2 binding increases the dynamics of their core helices, priming spikes for fusion. Conversely, substitutions in omicron spike lead to predominantly closed conformations, presumably enabling it to escape antibodies. At the same time, its core helices show characteristics of being pre-primed for fusion even in the absence of ACE2. These data inform on SARS-CoV-2 evolution and omicron variant emergence.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36745-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36745-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-36745-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().