7u0l
Crystal structure of the CCoV-HuPn-2018 RBD (domain B) in complex with canine APN
Structural highlights
FunctionAMPN_CANLF Broad specificity aminopeptidase which plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Also involved in the processing of various peptides including peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines. May also be involved the cleavage of peptides bound to major histocompatibility complex class II molecules of antigen presenting cells. May have a role in angiogenesis and promote cholesterol crystallization. May have a role in amino acid transport by acting as binding partner of amino acid transporter SLC6A19 and regulating its activity (By similarity).[UniProtKB:P15144][UniProtKB:P97449] (Microbial infection) Probable receptor for canine coronavirus (CCoV).[1] 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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