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

Autor: Sören von Bülow, Michael D. Mühlebach, Andre Schwarz, Sonja Welsch, Nayara Trevisan Doimo de Azevedo, Ger van Zandbergen, Florian Blanc, Shyamal Mosalaganti, Jonathan J M Landry, Katrin Bagola, Martin Beck, Wim J. H. Hagen, Mateusz Sikora, Christoph Schürmann, Cindy Hörner, Roberto Covino, Michael Gecht, Jacomine Krijnse Locker, Gerhard Hummer, Beata Turoňová
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Science (New York, N.y.)
Science
Signal Transduction and Targeted Therapy
ISSN: 1095-9203
0036-8075
Popis: 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.
Databáze: OpenAIRE
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