The human coronavirus HCoV‐229E S‐protein structure and receptor binding
- University of Toronto, Canada
- INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, Université du Québec, Canada
- The Hospital for Sick Children Research Institute, Canada
Abstract
The coronavirus S-protein mediates receptor binding and fusion of the viral and host cell membranes. In HCoV-229E, its receptor binding domain (RBD) shows extensive sequence variation but how S-protein function is maintained is not understood. Reported are the X-ray crystal structures of Class III-V RBDs in complex with human aminopeptidase N (hAPN), as well as the electron cryomicroscopy structure of the 229E S-protein. The structures show that common core interactions define the specificity for hAPN and that the peripheral RBD sequence variation is accommodated by loop plasticity. The results provide insight into immune evasion and the cross-species transmission of 229E and related coronaviruses. We also find that the 229E S-protein can expose a portion of its helical core to solvent. This is undoubtedly facilitated by hydrophilic subunit interfaces that we show are conserved among coronaviruses. These interfaces likely play a role in the S-protein conformational changes associated with membrane fusion.
Data availability
The X-ray diffraction data and X-ray crystal structures have been deposited in PDB under accession codes 6U7E, 6U7F and 6U7G. The cryo-EM map has been deposited in EMDB under accession code EMD-20668. The cryo-EM structure has been deposited in PDB under accession code 6U7H.
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X-ray diffraction data and X-ray crystal structuresProtein Data Bank, 6U7E.
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X-ray diffraction data and X-ray crystal structuresProtein Data Bank, 6U7F.
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X-ray diffraction data and X-ray crystal structuresProtein Data Bank, 6U7G.
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cryo-EM mapElectron Microsopy Data Bank, EMD-20668.
Article and author information
Author details
Funding
Canadian Institutes of Health Research
- James M Rini
Canadian Institutes of Health Research
- John L Rubinstein
Canadian Institutes of Health Research
- Pierre J Talbot
Canada Research Chairs
- John L Rubinstein
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Pamela J Bjorkman, California Institute of Technology, United States
Version history
- Received: August 20, 2019
- Accepted: October 12, 2019
- Accepted Manuscript published: October 25, 2019 (version 1)
- Version of Record published: January 20, 2020 (version 2)
Copyright
© 2019, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The human coronavirus HCoV‐229E S‐protein structure and receptor binding
eLife 8:e51230.
https://doi.org/10.7554/eLife.51230
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