The murine coronavirus hemagglutinin-esterase receptor-binding site: a major shift in ligand specificity through modest changes in architecture

• Published in: PLoS pathogens Vol. 8; no. 1; p. e1002492
• Main Authors: Langereis, Martijn A, Zeng, Qinghong, Heesters, Balthasar A, Heesters, Balthasar, Huizinga, Eric G, de Groot, Raoul J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2012; Public Library of Science (PLoS)
• Subjects: Acids; Animals; Architecture; Binding Sites; Biology; Carbon; Coronaviruses; Crystallography, X-Ray; Esterases; Health aspects; Hemagglutinins, Viral - chemistry; Hemagglutinins, Viral - metabolism; Hepatitis; Humans; Ligands; Ligands (Biochemistry); Materials Science; Mice; Murine hepatitis virus - chemistry; Murine hepatitis virus - physiology; N-Acetylneuraminic Acid - chemistry; N-Acetylneuraminic Acid - metabolism; Physiological aspects; Proteins; Rats; Rats, Wistar; Receptors, Virus - chemistry; Receptors, Virus - metabolism; Viral Fusion Proteins - chemistry; Viral Fusion Proteins - metabolism; Viral Tropism - physiology; Viruses; Netherlands
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1002492

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.