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

Autor: Calvaresi V; Department of Chemistry, King's College London, SE1 1DB, London, UK. valeria.clavaresi@kcl.ac.uk., Wrobel AG; Structural Biology of Disease Processes Laboratory, The Francis Crick Institute, NW1 1AT, London, UK. antoni.wrobel@crick.ac.uk., Toporowska J; Department of Chemistry, King's College London, SE1 1DB, London, UK., Hammerschmid D; Department of Chemistry, King's College London, SE1 1DB, London, UK., Doores KJ; Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, SE1 9RT, London, UK., Bradshaw RT; Department of Chemistry, King's College London, SE1 1DB, London, UK., Parsons RB; Department of Chemistry, King's College London, SE1 1DB, London, UK., Benton DJ; Structural Biology of Disease Processes Laboratory, The Francis Crick Institute, NW1 1AT, London, UK., Roustan C; Structural Biology Science Technology Platform, The Francis Crick Institute, NW1 1AT, London, UK., Reading E; Department of Chemistry, King's College London, SE1 1DB, London, UK., Malim MH; Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, SE1 9RT, London, UK., Gamblin SJ; Structural Biology of Disease Processes Laboratory, The Francis Crick Institute, NW1 1AT, London, UK., Politis A; Department of Chemistry, King's College London, SE1 1DB, London, UK. argyris.politis@manchester.ac.uk.; Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, M13 9PT, Manchester, UK. argyris.politis@manchester.ac.uk.; Manchester Institute of Biotechnology, The University of Manchester, M1 7DN, Manchester, UK. argyris.politis@manchester.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Mar 14; Vol. 14 (1), pp. 1421. Date of Electronic Publication: 2023 Mar 14.
DOI: 10.1038/s41467-023-36745-0
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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