title: The murine coronavirus hemagglutinin-esterase receptor-binding site: a major shift in ligand specificity through modest changes in architecture.
abstract: The hemagglutinin-esterases (HEs), envelope glycoproteins of corona-, toro- and orthomyxoviruses, mediate reversible virion attachment to O-acetylated sialic acids (O-Ac-Sias). They do so through concerted action of distinct receptor-binding ("lectin") and receptor-destroying sialate O-acetylesterase ("esterase") domains. Most HEs target 9-O-acetylated Sias. In one lineage of murine coronaviruses, however, HE esterase substrate and lectin ligand specificity changed dramatically as these viruses evolved to use 4-O-acetylated Sias instead. Here we present the crystal structure of the lectin domain of mouse hepatitis virus (MHV) strain S HE, resolved both in its native state and in complex with a receptor analogue. The data show that the shift from 9-O- to 4-O-Ac-Sia receptor usage primarily entailed a change in ligand binding topology and, surprisingly, only modest changes in receptor-binding site architecture. Our findings illustrate the ease with which viruses can change receptor-binding specificity with potential consequences for host-, organ and/or cell tropism, and for pathogenesis.
authors.affiliation: Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Martijn A
authors.initials: MA
authors.lastname: Langereis
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Zeng
authors.forename: Balthasar A
authors.initials: BA
authors.lastname: Heesters
authors.forename: Balthasar
authors.initials: B
authors.lastname: Heesters
authors.forename: Eric G
authors.initials: EG
authors.lastname: Huizinga
authors.forename: Raoul J
authors.initials: RJ
authors.lastname: de Groot
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D051379:Mice; D006517:Murine hepatitis virus / Q000737:chemistry* / Q000502:physiology; D019158:N-Acetylneuraminic Acid / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000378:metabolism; D056189:Viral Tropism / Q000502:physiology
chemical_list: D006389:Hemagglutinins, Viral; D011991:Receptors, Virus; D014760:Viral Fusion Proteins; C060814:hemagglutinin esterase; D019158:N-Acetylneuraminic Acid