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

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…

• VU
  Vanderbilt University
• JL
  Justus Liebig Universität Gießen
• EM
  European Molecular Biology Laboratory
• HF
  Human Frontier Science Program

  Award: RGP0026/2017
• AS
  Austrian Science Fund

  Awards: J4332-B28, Schroedinger Fellowship, J4332-B28
• M
  Max-Planck-Gesellschaft
• L
  Leibniz-Gemeinschaft
• L
  Leibniz-Rechenzentrum