Structural basis for ligand and substrate recognition by torovirus hemagglutinin esterases

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Title Structural basis for ligand and substrate recognition by torovirus hemagglutinin esterases
Author Langereis, Martijn A.; Zeng, Qinghong; Gerwig, Gerrit J.; Frey, Barbara; von Itzstein, Mark; Kamerling, Johannis P.; Groot, Raoul J. de; Huizinga, Eric G.
Journal Name Proceedings of the National Academy of Sciences of the United States of America
Year Published 2009
Place of publication United States
Publisher National Academy of Sciences
Abstract Hemagglutinin 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.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1073/pnas.0904266106
Volume 106
Issue Number 37
Page from 15897
Page to 15902
ISSN 0027-8424
Date Accessioned 2010-02-18
Date Available 2010-08-25T07:02:24Z
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Characterisation of Biological Macromolecules
URI http://hdl.handle.net/10072/30366
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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