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

Journal Article · · eLife
DOI:https://doi.org/10.7554/elife.51230· OSTI ID:1837244
 [1];  [2];  [2];  [1];  [3];  [3];  [4];  [5];  [6]
  1. Univ. of Toronto, ON (Canada). Dept. of Molecular Genetics
  2. Univ. of Toronto, ON (Canada). Dept. of Biochemistry
  3. Univ. of Quebec, Quebec City, QC (Canada). Lab. of Neuroimmunovirology. INRS-Inst. Armand-Frappier. Inst. National de la Recherche Scientifique
  4. The Hospital for Sick Children Research Inst., Toronto, ON (Canada). Molecular Medicine Program
  5. Univ. of Toronto, ON (Canada). Dept. of Biochemistry. Dept. of Medical Biophysics; The Hospital for Sick Children Research Inst., Toronto, ON (Canada). Molecular Medicine Program
  6. Univ. of Toronto, ON (Canada). Dept. of Molecular Genetics. Dept. of Biochemistry
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.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC)
OSTI ID:
1837244
Alternate ID(s):
OSTI ID: 1845544
Journal Information:
eLife, Journal Name: eLife Vol. 8; ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.Copyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Cited By (2)

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein journal April 2020
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein journal December 2020

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