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

Science. 2020 Oct 9;370(6513):203-208. doi: 10.1126/science.abd5223. Epub 2020 Aug 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Betacoronavirus / chemistry*
  • Cryoelectron Microscopy
  • Electron Microscope Tomography
  • Glycosylation
  • Humans
  • Molecular Dynamics Simulation*
  • Protein Domains
  • Protein Multimerization
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / chemistry*


  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2