In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges

  • The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the major focus for vaccine development. We combine cryo electron tomography, subtomogram averaging and molecular dynamics simulations to structurally analyze S in situ. Compared to recombinant S, the viral S is more heavily glycosylated and occurs predominantly in a closed pre-fusion conformation. We show that the stalk domain of S contains three hinges that give the globular domain unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and the development of safe vaccines. The large scale tomography data set of SARS-CoV-2 used for this study is therefore sufficient to resolve structural features to below 5 Ångstrom, and is publicly available at EMPIAR-10453.

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Author:Beata TuroňováORCiD, Mateusz SikoraORCiD, Christoph SchürmannORCiDGND, Wim HagenORCiDGND, Sonja WelschORCiDGND, Florian E. C. BlancORCiD, Sören von BülowORCiDGND, Michael GechtORCiDGND, Katrin BagolaORCiDGND, Cindy HörnerORCiDGND, Ger van ZandbergenORCiDGND, Shyamal Narayan MosalagantiORCiDGND, Andre SchwarzORCiDGND, Roberto CovinoORCiD, Michael D. MühlebachORCiDGND, Gerhard HummerORCiD, Jacomine Krijnse-LockerORCiDGND, Martin BeckORCiDGND
Parent Title (English):bioRxiv
Document Type:Preprint
Date of Publication (online):2020/07/11
Date of first Publication:2020/07/11
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/06/15
Page Number:22
Wissenschaftliche Zentren und koordinierte Programme / Frankfurt Institute for Advanced Studies (FIAS)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International