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Nature. 2016 Mar 3;531(7592):114-117. doi: 10.1038/nature16988. Epub 2016 Feb 8.

Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer.

Author information

1
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
2
Institut Pasteur, Unité de Virologie Structurale, Paris, France.
3
CNRS UMR 3569 Virologie, Paris, France.
4
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
#
Contributed equally

Abstract

The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor-binding and membrane fusion functions. S also contains the principal antigenic determinants and is the target of neutralizing antibodies. Here we present the structure of a mouse coronavirus S trimer ectodomain determined at 4.0 Å resolution by single particle cryo-electron microscopy. It reveals the metastable pre-fusion architecture of S and highlights key interactions stabilizing it. The structure shares a common core with paramyxovirus F proteins, implicating mechanistic similarities and an evolutionary connection between these viral fusion proteins. The accessibility of the highly conserved fusion peptide at the periphery of the trimer indicates potential vaccinology strategies to elicit broadly neutralizing antibodies against coronaviruses. Finally, comparison with crystal structures of human coronavirus S domains allows rationalization of the molecular basis for species specificity based on the use of spatially contiguous but distinct domains.

PMID:
26855426
PMCID:
PMC5018210
DOI:
10.1038/nature16988
[Indexed for MEDLINE]
Free PMC Article

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