Structures, conformations and distributions of SARS-CoV-2 spike protein trimers on intact virions

Ke, Z.; Oton, J.; Qu, K.; Cortese, M.; Zila, V.; McKeane, L.; Nakane, T.; Zivanov, J.; Neufeldt, C. J.; Lu, J. M.; Peukes, J.; Xiong, X.; Krausslich, H.-G.; Scheres, S. H. W.; Bartenschlager, R.; Briggs, J. A. G.

doi:10.1101/2020.06.27.174979

bioRxiv · 10.1101/2020.06.27.174979

Structures, conformations and distributions of SARS-CoV-2 spike protein trimers on intact virions

Ke, Z.·Oton, J.·Qu, K.·Cortese, M.·Zila, V.·McKeane, L.·Nakane, T.·Zivanov, J.·Neufeldt, C. J.·Lu, J. M.·Peukes, J.·Xiong, X.·Krausslich, H.-G.·Scheres, S. H. W.·Bartenschlager, R.·Briggs, J. A. G.

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude. Heavily glycosylated S trimers bind the ACE2 receptor and mediate entry of virions into target cells. S exhibits extensive conformational flexibility: it modulates the exposure of its receptor binding site and later undergoes complete structural rearrangement to drive fusion of viral and cellular membranes. The structures and conformations of soluble, overexpressed, purified S proteins have been studied in detail using cryo-electron microscopy. The structure and distribution of S on the virion surface, however, has not been characterised. Here we applied cryo-electron microscopy and tomography to image intact SARS-CoV-2 virions, determining the high-resolution structure, conformational flexibility and distributions of S trimers in situ on the virion surface. These results provide a basis for understanding the conformations of S present on the virion, and for studying their interactions with neutralizing antibodies.

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Ke, Z., Oton, J., Qu, K., Cortese, M., Zila, V., McKeane, L., Nakane, T., Zivanov, J., Neufeldt, C. J., Lu, J. M., Peukes, J., Xiong, X., Krausslich, H.-G., Scheres, S. H. W., Bartenschlager, R., Briggs, J. A. G.. 2020-06-27. Structures, conformations and distributions of SARS-CoV-2 spike protein trimers on intact virions. https://doi.org/10.1101/2020.06.27.174979

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