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...

Descripción completa

Detalles Bibliográficos
Autores principales: Turoňová, Beata, Sikora, Mateusz, Schürmann, Christoph, Hagen, Wim J. H., Welsch, Sonja, Blanc, Florian E. C., von Bülow, Sören, Gecht, Michael, Bagola, Katrin, Hörner, Cindy, van Zandbergen, Ger, Landry, Jonathan, de Azevedo, Nayara Trevisan Doimo, Mosalaganti, Shyamal, Schwarz, Andre, Covino, Roberto, Mühlebach, Michael D., Hummer, Gerhard, Krijnse Locker, Jacomine, Beck, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665311/
https://www.ncbi.nlm.nih.gov/pubmed/32817270
http://dx.doi.org/10.1126/science.abd5223
Descripción
Sumario: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.

Ejemplares similares