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Cryo-EM structure of the HCoV-229E spike glycoproteinCryo-EM structure of the HCoV-229E spike glycoprotein
Structural highlights
FunctionSPIKE_CVH22 S1 region attaches the virion to the cell membrane by interacting with human ANPEP/aminopeptidase N, initiating the infection. Binding to the receptor probably induces conformational changes in the S glycoprotein unmasking the fusion peptide of S2 region and activating membranes fusion. S2 region belongs to the class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes (By similarity). Publication Abstract from PubMedThe 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. The human coronavirus HCoV-229E S-protein structure and receptor binding.,Li Z, Tomlinson ACA, Wong AHM, Zhou D, Desforges M, Talbot PJ, Benlekbir S, Rubinstein JL, Rini JM Elife. 2019 Oct 25;8. pii: 51230. doi: 10.7554/eLife.51230. PMID:31650956[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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