Zunlong Ke1, Joaquin Oton1, Kun Qu1, Mirko Cortese2, Vojtech Zila3, Lesley McKeane4, Takanori Nakane1, Jasenko Zivanov1, Christopher J Neufeldt2, Berati Cerikan2, John M Lu1, Julia Peukes1, Xiaoli Xiong1, Hans-Georg Kräusslich3,5, Sjors H W Scheres1, Ralf Bartenschlager2,5,6, John A G Briggs7. 1. Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK. 2. Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany. 3. Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg, Germany. 4. Visual Aids Department, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK. 5. German Center for Infection Research, Heidelberg Partner Site, Heidelberg, Germany. 6. Division of Virus-Associated Carcinogenesis, German Cancer Research Center (DKFZ), Heidelberg, Germany. 7. Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK. jbriggs@mrc-lmb.cam.ac.uk.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude1. Heavily glycosylated S trimers bind to the angiotensin-converting enzyme 2 receptor and mediate entry of virions into target cells2-6. S exhibits extensive conformational flexibility: it modulates exposure of its receptor-binding site and subsequently undergoes complete structural rearrangement to drive fusion of viral and cellular membranes2,7,8. The structures and conformations of soluble, overexpressed, purified S proteins have been studied in detail using cryo-electron microscopy2,7,9-12, but the structure and distribution of S on the virion surface remain unknown. Here we applied cryo-electron microscopy and tomography to image intact SARS-CoV-2 virions and determine the high-resolution structure, conformational flexibility and distribution of S trimers in situ on the virion surface. These results reveal the conformations of S on the virion, and provide a basis from which to understand interactions between S and neutralizing antibodies during infection or vaccination.
Severe acute respiratory syndrome coronavirus 2 (n class="Species">SARS-CoV-2) virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude1. Heavily glycosylated S trimers bind to the angiotensin-converting enzyme 2 receptor and mediate entry of virions into target cells2-6. S exhibits extensive conformational flexibility: it modulates exposure of its receptor-binding site and subsequently undergoes complete structural rearrangement to drive fusion of viral and cellular membranes2,7,8. The structures and conformations of soluble, overexpressed, purified S proteins have been studied in detail using cryo-electron microscopy2,7,9-12, but the structure and distribution of S on the virion surface remain unknown. Here we applied cryo-electron microscopy and tomography to image intact SARS-CoV-2 virions and determine the high-resolution structure, conformational flexibility and distribution of S trimers in situ on the virion surface. These results reveal the conformations of S on the virion, and provide a basis from which to understand interactions between S and neutralizing antibodies during infection or vaccination.
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