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

Turonova, B.; Sikora, M.; Schürmann, C.; Hagen, W. J. H.; Welsch, S.; Blanc, F. E. C.; von Bülow, S.; Gecht, M.; Bagola, K.; Hörner, C.; van Zandbergen, G.; Mosalaganti, S.; Schwarz, A.; Covino, R.; Mühlebach, M. D.; Hummer, G.; Krijnse Locker, J.; Beck, M.

doi:10.1101/2020.06.26.173476

bioRxiv · 10.1101/2020.06.26.173476

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

Turonova, B.·Sikora, M.·Schürmann, C.·Hagen, W. J. H.·Welsch, S.·Blanc, F. E. C.·von Bülow, S.·Gecht, M.·Bagola, K.·Hörner, C.·van Zandbergen, G.·Mosalaganti, S.·Schwarz, A.·Covino, R.·Mühlebach, M. D.·Hummer, G.·Krijnse Locker, J.·Beck, M.

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Abstract

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the major focus for vaccine development. We combine cryo electron tomography, subtomogram averaging and molecular dynamics simulations to structurally analyze S in situ. Compared to recombinant S, the viral S is more heavily glycosylated and occurs predominantly in a closed pre-fusion conformation. We show that the stalk domain of S contains three hinges that give the globular domain 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 the development of safe vaccines. The large scale tomography data set of SARS-CoV-2 used for this study is therefore sufficient to resolve structural features to below 5 [A]ngstrom, and is publicly available at EMPIAR-10453.

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Turonova, B., Sikora, M., Schürmann, C., Hagen, W. J. H., Welsch, S., Blanc, F. E. C., von Bülow, S., Gecht, M., Bagola, K., Hörner, C., van Zandbergen, G., Mosalaganti, S., Schwarz, A., Covino, R., Mühlebach, M. D., Hummer, G., Krijnse Locker, J., Beck, M.. 2020-06-26. In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges. https://doi.org/10.1101/2020.06.26.173476

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