Crucial steps in the structure determination of a coronavirus spike glycoprotein using cryo-electron microscopy.
The tremendous pandemic potential of coronaviruses was demonstrated twice in the last 15 years 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. Despite their biomedical importance, coronavirus S glycoproteins have proven difficult targets for structural characterization, precluding high-resolution studies of the biologically relevant trimer. Recent technological developments in single particle cryo-electron microscopy allowed us to determine the first structure of a coronavirus S glycoprotein trimer which provided a framework to understand the mechanisms of viral entry and suggested potential inhibition strategies for this family of viruses. Here, we describe the key factors that enabled this breakthrough.
Department of Biochemistry, University of Washington, Seattle, Washington, 98195.
Alexandra
A
Walls
Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.|CNRS UMR 3569 Virologie, Paris, France.
M Alejandra
MA
Tortorici
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.
Berend-Jan
BJ
Bosch
Department of Biochemistry, University of Washington, Seattle, Washington, 98195.
Brandon
B
Frenz
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.
Peter J M
PJ
Rottier
Department of Biochemistry, University of Washington, Seattle, Washington, 98195.
Frank
F
DiMaio
Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, Paris, France.|CNRS UMR 3569 Virologie, Paris, France.
Felix A
FA
Rey
Department of Biochemistry, University of Washington, Seattle, Washington, 98195.
David
D
Veesler
D020285:Cryoelectron Microscopy / Q000379:methods*; D065207:Middle East Respiratory Syndrome Coronavirus / Q000737:chemistry / Q000648:ultrastructure*; D008958:Models, Molecular; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D064370:Spike Glycoprotein, Coronavirus / Q000737:chemistry / Q000648:ultrastructure*
D064370:Spike Glycoprotein, Coronavirus
coronavirus spike protein; cryo-electron microscopy; rational vaccine design; relion; rosetta
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