In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges
By Beata Turoňová, M. Sikora, Christoph Schürmann, W. Hagen, Sonja Welsch, Florian E. C. Blanc, Sören von Bülow, Michael Gecht, Katrin Bagola, Cindy Hörner and 10 more. Science, 2020
598 citations recorded by the source corpus.
Flexible spikes The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein enables viral entry into host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor and is a major target for neutralizing antibodies. About 20 to 40 spikes decorate the surface of virions. Turoňová et al. now show that the spike is flexibly connected to the viral surface by three hinges that are well protected by glycosylation sites. The flexibility imparted by these hinges may explain how multiple spikes act in concert to engage onto the flat surface of a host cell. Science, this issue p. 203 Flexible hinges shielded by glycans in the coronavirus spike protein may allow scanning of the host cell surface. 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.
Subfields: Infectious Diseases, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/f46b30c34b8c3c7da64367b2df69c89e527d2204
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In Infectious Diseases
Citations in the corpus
- AreTomo: An integrated software package for automated marker-free, motion-corrected cryo-electron tomographic alignment and reconstruction (2022, methodology): “In one current example, the structures of the SARS-Cov-2 spike proteins were published with a map of the spike head at 7.9Å resolution and a map of the closed conformation at 4.9Å resolution (Turoňová et al., 2020).”
- Controlling the SARS-CoV-2 spike glycoprotein conformation (2020, unknown): “Indeed, full-length SARS-CoV-2 spike structures, either detergent solubilized 37 or virion associated 38 , suggest the ‘down’ state is the predominant state which, in a vaccination context, may limit RBD-directed responses.”
- Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology (2020, unknown): “…SARS-CoV-2 entry into host cells is mediated by the transmembrane spike (S) glycoprotein, which forms prominent homotrimers protruding from the viral surface (Ke et al., 2020; Tortorici and Veesler, 2019; Turo (cid:1) nova´ al., 2020; Walls et al., 2016a; 2017). of nAbs against SARS-CoV-2.”
- Structure-guided covalent stabilization of coronavirus spike glycoprotein trimers in the closed conformation (2020, unknown): “Recent reports of the observation of postfusion trimers at the surface of purified authentic SARS-CoV-2 58–60 and of spontaneous refolding of a fraction of S trimers upon detergent-solubilization 61 showcase these limitations.”