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dc.contributor.authorA. Langereis, Martijnen_US
dc.contributor.authorZeng, Qinghongen_US
dc.contributor.authorJ. Gerwig, Gerriten_US
dc.contributor.authorFrey, Barbaraen_US
dc.contributor.authorvon Itzstein, Marken_US
dc.contributor.authorP. Kamerling, Johannisen_US
dc.contributor.authorJ. de Groot, Raoulen_US
dc.contributor.authorG. Huizinga, Ericen_US
dc.description.abstractHemagglutinin esterases (HEs), closely related envelope glycoproteins in influenza C and corona- and toroviruses, mediate reversible attachment to O-acetylated sialic acids (Sias). They do so by acting both as lectins and as receptor-destroying enzymes, functions exerted by separate protein domains. HE divergence was accompanied by changes in quaternary structure and in receptor and substrate specificity. The selective forces underlying HE diversity and the molecular basis for Sia specificity are poorly understood.Herewe present crystal structures of porcine and bovine torovirus HEs in complex with receptor analogs. Torovirus HEs form homodimers with sialate-Oacetylesterase domains almost identical to corresponding domains in orthomyxo- and coronavirus HEs, but with unique lectin sites. Structure- guided biochemical analysis of the esterase domains revealed that a functionally, but not structurally conserved arginine-Sia carboxylate interaction is critical for the binding and positioning of glycosidically bound Sias in the catalytic pocket. Although essential for efficient de-O-acetylation of Sias, this interaction is not required for catalysis nor does it affect substrate specificity. In fact, the distinct preference of the porcine torovirus enzyme for 9-mono- over 7,9-di- O-acetylated Sias can be explained from a single-residue difference with HEs of more promiscuous specificity. Apparently, esterase and lectin pockets coevolved; also the porcine torovirus HE receptorbinding site seems to have been designed to use 9-mono- and exclude di-O-acetylated Sias, possibly as an adaptation to replication in swine. Our findings shed light on HE evolution and provide fundamental insight into mechanisms of substrate binding, substrate recognition, and receptor selection in this important class of virion proteins.en_US
dc.publisherNational Academy of Sciencesen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofjournalProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subject.fieldofresearchCharacterisation of Biological Macromoleculesen_US
dc.titleStructural basis for ligand and substrate recognition by torovirus hemagglutinin esterasesen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.hasfulltextNo Full Text

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