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Title: An electrostatically-steered conformational selection mechanism promotes SARS-CoV-2 spike protein variation
Author(s): Sorokina, Marija
Belapure, Jaydeep
Tüting, Christian
Paschke, Reinhard
Papasotiriou, Ioannis
Rodrigues, João P.G.L.M.
Kastritis, Panagiotis L.
Issue Date: 2022
Type: Article
Language: English
Abstract: After two years since the outbreak, the COVID-19 pandemic remains a global public health emergency. SARS-CoV-2 variants with substitutions on the spike (S) protein emerge increasing the risk of immune evasion and cross-species transmission. Here, we analyzed the evolution of the S protein as recorded in 276,712 samples collected before the start of vaccination efforts. Our analysis shows that most variants destabilize the S protein trimer, increase its conformational heterogeneity and improve the odds of the recognition by the host cell receptor. Most frequent substitutions promote overall hydrophobicity by replacing charged amino acids, reducing stabilizing local interactions in the unbound S protein trimer. Moreover, our results identify “forbidden” regions that rarely show any sequence variation, and which are related to conformational changes occurring upon fusion. These results are significant for understanding the structure and function of SARS-CoV-2 related proteins which is a critical step in vaccine development and epidemiological surveillance.
Open Access: Open access publication
License: (CC BY 4.0) Creative Commons Attribution 4.0(CC BY 4.0) Creative Commons Attribution 4.0
Sponsor/Funder: Publikationsfonds MLU
Journal Title: Journal of molecular biology
Publisher: Elsevier
Publisher Place: Amsterdam [u.a.]
Volume: 434
Issue: 13
Original Publication: 10.1016/j.jmb.2022.167637
Appears in Collections:Open Access Publikationen der MLU

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