In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges.
Beata TuroňováMateusz SikoraChristoph SchürmannWim J H HagenSonja WelschFlorian E C BlancSören von BülowMichael GechtKatrin BagolaCindy HörnerGer van ZandbergenJonathan J M LandryNayara Trevisan Doimo de AzevedoShyamal MosalagantiAndre SchwarzRoberto CovinoMichael D MühlebachGerhard HummerJacomina Krijnse LockerMartin BeckPublished in: Science (New York, N.Y.) (2020)
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.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- molecular dynamics simulations
- cell surface
- molecular docking
- coronavirus disease
- electron microscopy
- computed tomography
- single cell
- high resolution
- stem cells
- magnetic resonance imaging
- mass spectrometry
- optical coherence tomography
- magnetic resonance
- mesenchymal stem cells
- crystal structure
- dual energy
- solar cells