3i26 | pdb_00003i26
Structure of bovine torovirus Hemagglutinin-Esterase
Structural highlights
Function[HEMA_BRV1] Structural protein that makes short spikes at the surface of the virus. Contains receptor binding and receptor-destroying activities. Mediates de-O-acetylation of N-acetyl-9-di-O-acetylneuraminic acid, which is probably the receptor determinant recognized by the virus on the surface of erythrocytes and susceptible cells. Also hydrolyzes 5-N-acetyl-4-O-acetylneuramic acid and N-acetyl-9-O-acetylneuraminic acid, but displays a substrate preference for N-acetyl-9-di-O-acetylneuraminic acid. This receptor-destroying activity is important for virus release as it probably helps preventing self-aggregation and ensures the efficient spread of the progeny virus from cell to cell. May serve as a secondary viral attachment protein for initiating infection, the spike protein being the major one. Seems to be a 'luxury' protein that is not absolutely necessary for virus infection in culture. However, its presence in the virus may alter its pathogenicity. May become a target for both the humoral and the cellular branches of the immune system. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHemagglutinin 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. Here we present crystal structures of porcine and bovine torovirus HEs in complex with receptor analogs. Torovirus HEs form homodimers with sialate-O-acetylesterase 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 receptor-binding 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. Structural basis for ligand and substrate recognition by torovirus hemagglutinin esterases.,Langereis MA, Zeng Q, Gerwig GJ, Frey B, von Itzstein M, Kamerling JP, de Groot RJ, Huizinga EG Proc Natl Acad Sci U S A. 2009 Aug 31. PMID:19721004[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences | ||||||||||||||||||||||||
