7us9
From Proteopedia
CCoV-HuPn-2018 S in the proximal conformation (local refinement of domain 0)
Structural highlights
FunctionA0A8E6CMP0_9ALPC S1 region attaches the virion to the cell membrane by interacting with the host receptor, 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.[HAMAP-Rule:MF_04200] Publication Abstract from PubMedThe isolation of CCoV-HuPn-2018 from a child respiratory swab indicates that more coronaviruses are spilling over to humans than previously appreciated. We determined the structures of the CCoV-HuPn-2018 spike glycoprotein trimer in two distinct conformational states and showed that its domain 0 recognizes sialosides. We identified that the CCoV-HuPn-2018 spike binds canine, feline, and porcine aminopeptidase N (APN) orthologs, which serve as entry receptors, and determined the structure of the receptor-binding B domain in complex with canine APN. The introduction of an oligosaccharide at position N739 of human APN renders cells susceptible to CCoV-HuPn-2018 spike-mediated entry, suggesting that single-nucleotide polymorphisms might account for viral detection in some individuals. Human polyclonal plasma antibodies elicited by HCoV-229E infection and a porcine coronavirus monoclonal antibody inhibit CCoV-HuPn-2018 spike-mediated entry, underscoring the cross-neutralizing activity among a-coronaviruses. These data pave the way for vaccine and therapeutic development targeting this zoonotic pathogen representing the eighth human-infecting coronavirus. Structure, receptor recognition, and antigenicity of the human coronavirus CCoV-HuPn-2018 spike glycoprotein.,Tortorici MA, Walls AC, Joshi A, Park YJ, Eguia RT, Miranda MC, Kepl E, Dosey A, Stevens-Ayers T, Boeckh MJ, Telenti A, Lanzavecchia A, King NP, Corti D, Bloom JD, Veesler D Cell. 2022 Jun 23;185(13):2279-2291.e17. doi: 10.1016/j.cell.2022.05.019. Epub , 2022 May 27. PMID:35700730[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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