In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges
Beata Turoňová, Mateusz Sikora, Christoph Schürmann, Wim J. H. Hagen, Sonja Welsch, Florian E.C. Blanc, Sören von Bülow, Michael Gecht, Katrin Bagola, Cindy Hörner, Ger van Zandbergen, Jonathan J. M. Landry, Nayara Azevedo, Shyamal Mosalaganti, Andre Schwarz, Roberto Covino, Michael D. Mühlebach, Gerhard Hummer, Jacomine Krijnse Locker, Martin Beck
Abstract
The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the primary focus for vaccine development. In this study, we combined cryo-electron tomography, subtomogram averaging, and molecular dynamics simulations to structurally analyze S in situ. Compared with the recombinant S, the viral S was more heavily glycosylated and occurred mostly in the closed prefusion conformation. We show that the stalk domain of S contains three hinges, giving the head 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 potentially to the development of safe vaccines.