The human coronavirus HCoV‐229E S‐protein structure and receptor binding

  1. Zhijie Li
  2. Aidan C A Tomlinson
  3. Alan H M Wong
  4. Dongxia Zhou
  5. Marc Desforges
  6. Pierre J Talbot
  7. Samir Benlekbir
  8. John L Rubinstein
  9. James M Rini  Is a corresponding author
  1. University of Toronto, Canada
  2. INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, Université du Québec, Canada
  3. 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.

The following data sets were generated

Article and author information

Author details

  1. Zhijie Li

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9283-6072
  2. Aidan C A Tomlinson

    Department of Biochemistry, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Alan H M Wong

    Department of Biochemistry, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Dongxia Zhou

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Marc Desforges

    Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, Université du Québec, Laval, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Pierre J Talbot

    Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, Université du Québec, Laval, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Samir Benlekbir

    Molecular Medicine Program, The Hospital for Sick Children Research Institute, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. John L Rubinstein

    Department of Biochemistry, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0566-2209
  9. James M Rini

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    For correspondence
    james.rini@utoronto.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0952-2409

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

  1. Pamela J Bjorkman, California Institute of Technology, United States

Publication history

  1. Received: August 20, 2019
  2. Accepted: October 12, 2019
  3. Accepted Manuscript published: October 25, 2019 (version 1)
  4. 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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  1. Zhijie Li
  2. Aidan C A Tomlinson
  3. Alan H M Wong
  4. Dongxia Zhou
  5. Marc Desforges
  6. Pierre J Talbot
  7. Samir Benlekbir
  8. John L Rubinstein
  9. James M Rini
(2019)
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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