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.
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
Further reading
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- Biochemistry and Chemical Biology
- Structural Biology and Molecular Biophysics
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Paramyxovirus membrane fusion requires an attachment protein for receptor binding and a fusion protein for membrane fusion triggering. Nipah virus (NiV) attachment protein (G) binds to ephrinB2 or -B3 receptors, and fusion protein (F) mediates membrane fusion. NiV-F is a class I fusion protein and is activated by endosomal cleavage. The crystal structure of a soluble GCN4-decorated NiV-F shows a hexamer-of-trimer assembly. Here, we used single-molecule localization microscopy to quantify the NiV-F distribution and organization on cell and virus-like particle membranes at a nanometer precision. We found that NiV-F on biological membranes forms distinctive clusters that are independent of endosomal cleavage or expression levels. The sequestration of NiV-F into dense clusters favors membrane fusion triggering. The nano-distribution and organization of NiV-F are susceptible to mutations at the hexamer-of-trimer interface, and the putative oligomerization motif on the transmembrane domain. We also show that NiV-F nanoclusters are maintained by NiV-F–AP-2 interactions and the clathrin coat assembly. We propose that the organization of NiV-F into nanoclusters facilitates membrane fusion triggering by a mixed population of NiV-F molecules with varied degrees of cleavage and opportunities for interacting with the NiV-G/receptor complex. These observations provide insights into the in situ organization and activation mechanisms of the NiV fusion machinery.
