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Structures and distributions of SARS-CoV-2 spike proteins on intact virions

Author

Listed:
  • Zunlong Ke

    (Medical Research Council Laboratory of Molecular Biology)

  • Joaquin Oton

    (Medical Research Council Laboratory of Molecular Biology)

  • Kun Qu

    (Medical Research Council Laboratory of Molecular Biology)

  • Mirko Cortese

    (Molecular Virology, Heidelberg University)

  • Vojtech Zila

    (Virology, Heidelberg University)

  • Lesley McKeane

    (Medical Research Council Laboratory of Molecular Biology)

  • Takanori Nakane

    (Medical Research Council Laboratory of Molecular Biology)

  • Jasenko Zivanov

    (Medical Research Council Laboratory of Molecular Biology)

  • Christopher J. Neufeldt

    (Molecular Virology, Heidelberg University)

  • Berati Cerikan

    (Molecular Virology, Heidelberg University)

  • John M. Lu

    (Medical Research Council Laboratory of Molecular Biology)

  • Julia Peukes

    (Medical Research Council Laboratory of Molecular Biology)

  • Xiaoli Xiong

    (Medical Research Council Laboratory of Molecular Biology)

  • Hans-Georg Kräusslich

    (Virology, Heidelberg University
    Heidelberg Partner Site)

  • Sjors H. W. Scheres

    (Medical Research Council Laboratory of Molecular Biology)

  • Ralf Bartenschlager

    (Molecular Virology, Heidelberg University
    Heidelberg Partner Site
    German Cancer Research Center (DKFZ))

  • John A. G. Briggs

    (Medical Research Council Laboratory of Molecular Biology)

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.

Suggested Citation

  • Zunlong Ke & Joaquin Oton & Kun Qu & Mirko Cortese & Vojtech Zila & Lesley McKeane & Takanori Nakane & Jasenko Zivanov & Christopher J. Neufeldt & Berati Cerikan & John M. Lu & Julia Peukes & Xiaoli X, 2020. "Structures and distributions of SARS-CoV-2 spike proteins on intact virions," Nature, Nature, vol. 588(7838), pages 498-502, December.
    • Handle: RePEc:nat:nature:v:588:y:2020:i:7838:d:10.1038_s41586-020-2665-2
    DOI: 10.1038/s41586-020-2665-2
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    1. Mathieu Claireaux & Tom G. Caniels & Marlon Gast & Julianna Han & Denise Guerra & Gius Kerster & Barbera D. C. Schaik & Aldo Jongejan & Angela I. Schriek & Marloes Grobben & Philip J. M. Brouwer & Kar, 2022. "A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
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    9. Kemin Tan & Junjian Chen & Yu Kaku & Yi Wang & Luke Donius & Rafiq Ahmad Khan & Xiaolong Li & Hannah Richter & Michael S. Seaman & Thomas Walz & Wonmuk Hwang & Ellis L. Reinherz & Mikyung Kim, 2023. "Inadequate structural constraint on Fab approach rather than paratope elicitation limits HIV-1 MPER vaccine utility," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
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    12. Bryan S. Sibert & Joseph Y. Kim & Jie E. Yang & Zunlong Ke & Christopher C. Stobart & Martin L. Moore & Elizabeth R. Wright, 2024. "Assembly of respiratory syncytial virus matrix protein lattice and its coordination with fusion glycoprotein trimers," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    13. David Chmielewski & Eric A. Wilson & Grigore Pintilie & Peng Zhao & Muyuan Chen & Michael F. Schmid & Graham Simmons & Lance Wells & Jing Jin & Abhishek Singharoy & Wah Chiu, 2023. "Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    14. Valeria Calvaresi & Antoni G. Wrobel & Joanna Toporowska & Dietmar Hammerschmid & Katie J. Doores & Richard T. Bradshaw & Ricardo B. Parsons & Donald J. Benton & Chloë Roustan & Eamonn Reading & Micha, 2023. "Structural dynamics in the evolution of SARS-CoV-2 spike glycoprotein," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    15. Qingqing Feng & Keman Cheng & Lizhuo Zhang & Dongshu Wang & Xiaoyu Gao & Jie Liang & Guangna Liu & Nana Ma & Chen Xu & Ming Tang & Liting Chen & Xinwei Wang & Xuehui Ma & Jiajia Zou & Quanwei Shi & Pe, 2024. "Rationally designed multimeric nanovaccines using icosahedral DNA origami for display of SARS-CoV-2 receptor binding domain," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    16. Zhiqiang Li & Han Xia & Guibo Rao & Yan Fu & Tingting Chong & Kexing Tian & Zhiming Yuan & Sheng Cao, 2024. "Cryo-EM structures of Banna virus in multiple states reveal stepwise detachment of viral spikes," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    17. Lei Peng & Yingxia Hu & Madeleine C. Mankowski & Ping Ren & Rita E. Chen & Jin Wei & Min Zhao & Tongqing Li & Therese Tripler & Lupeng Ye & Ryan D. Chow & Zhenhao Fang & Chunxiang Wu & Matthew B. Dong, 2022. "Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    18. Alexander J. Pak & Alvin Yu & Zunlong Ke & John A. G. Briggs & Gregory A. Voth, 2022. "Cooperative multivalent receptor binding promotes exposure of the SARS-CoV-2 fusion machinery core," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    19. Rong Zhu & Daniel Canena & Mateusz Sikora & Miriam Klausberger & Hannah Seferovic & Ahmad Reza Mehdipour & Lisa Hain & Elisabeth Laurent & Vanessa Monteil & Gerald Wirnsberger & Ralph Wieneke & Robert, 2022. "Force-tuned avidity of spike variant-ACE2 interactions viewed on the single-molecule level," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    20. Oskar Staufer & Kapil Gupta & Jochen Estebano Hernandez Bücher & Fabian Kohler & Christian Sigl & Gunjita Singh & Kate Vasileiou & Ana Yagüe Relimpio & Meline Macher & Sebastian Fabritz & Hendrik Diet, 2022. "Synthetic virions reveal fatty acid-coupled adaptive immunogenicity of SARS-CoV-2 spike glycoprotein," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    21. Peter J. Halfmann & Kathryn Loeffler & Augustine Duffy & Makoto Kuroda & Jie E. Yang & Elizabeth R. Wright & Yoshihiro Kawaoka & Ravi S. Kane, 2024. "Broad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    22. Nikhil Kumar Tulsian & Raghuvamsi Venkata Palur & Xinlei Qian & Yue Gu & Bhuvaneshwari D/O Shunmuganathan & Firdaus Samsudin & Yee Hwa Wong & Jianqing Lin & Kiren Purushotorman & Mary McQueen Kozma & , 2023. "Defining neutralization and allostery by antibodies against COVID-19 variants," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    23. Yinong Zhang & Yanxiang Cui & Jingchen Sun & Z. Hong Zhou, 2022. "Multiple conformations of trimeric spikes visualized on a non-enveloped virus," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    24. Tamara Kaleta & Lisa Kern & Samuel Leandro Hong & Martin Hölzer & Georg Kochs & Julius Beer & Daniel Schnepf & Martin Schwemmle & Nena Bollen & Philipp Kolb & Magdalena Huber & Svenja Ulferts & Sebast, 2022. "Antibody escape and global spread of SARS-CoV-2 lineage A.27," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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