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

Zunlong Ke, Joaquin Oton, Kun Qu, Mirko Cortese, Vojtech Zila, Lesley McKeane, Takanori Nakane, Jasenko Zivanov, Christopher J. Neufeldt, John M. Lu, Julia Peukes, Xiaoli Xiong, Hans-Georg Kräusslich, Sjors H.W. Scheres, Ralf Bartenschlager, View ORCID ProfileJohn A.G. Briggs
doi: https://doi.org/10.1101/2020.06.27.174979
Zunlong Ke
1Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
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Joaquin Oton
1Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
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Kun Qu
1Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
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Mirko Cortese
2Department of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany
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Vojtech Zila
3Department of Infectious Diseases, Virology, Heidelberg University, 69120 Heidelberg, Germany
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Lesley McKeane
4Visual Aids Department, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
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Takanori Nakane
1Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
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Jasenko Zivanov
1Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
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Christopher J. Neufeldt
2Department of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany
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John M. Lu
1Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
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Julia Peukes
1Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
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Xiaoli Xiong
1Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
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Hans-Georg Kräusslich
3Department of Infectious Diseases, Virology, Heidelberg University, 69120 Heidelberg, Germany
5German Center for Infection Research, Heidelberg partner site, 69120 Heidelberg, Germany
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Sjors H.W. Scheres
1Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
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Ralf Bartenschlager
2Department of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany
5German Center for Infection Research, Heidelberg partner site, 69120 Heidelberg, Germany
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John A.G. Briggs
1Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
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  • ORCID record for John A.G. Briggs
  • For correspondence: jbriggs@mrc-lmb.cam.ac.uk
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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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 27, 2020.
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Structures, conformations and distributions of SARS-CoV-2 spike protein trimers on intact virions
Zunlong Ke, Joaquin Oton, Kun Qu, Mirko Cortese, Vojtech Zila, Lesley McKeane, Takanori Nakane, Jasenko Zivanov, Christopher J. Neufeldt, John M. Lu, Julia Peukes, Xiaoli Xiong, Hans-Georg Kräusslich, Sjors H.W. Scheres, Ralf Bartenschlager, John A.G. Briggs
bioRxiv 2020.06.27.174979; doi: https://doi.org/10.1101/2020.06.27.174979
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Structures, conformations and distributions of SARS-CoV-2 spike protein trimers on intact virions
Zunlong Ke, Joaquin Oton, Kun Qu, Mirko Cortese, Vojtech Zila, Lesley McKeane, Takanori Nakane, Jasenko Zivanov, Christopher J. Neufeldt, John M. Lu, Julia Peukes, Xiaoli Xiong, Hans-Georg Kräusslich, Sjors H.W. Scheres, Ralf Bartenschlager, John A.G. Briggs
bioRxiv 2020.06.27.174979; doi: https://doi.org/10.1101/2020.06.27.174979

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