Download MendeleyThe Murine Coronavirus Hemagglutinin-Esterase Receptor-Binding Site: A Major Shift in Ligand Specificity Through Modest Changes in Architecture.
Langereis, M.A., Zeng, Q., Heesters, B.A., Huizinga, E.G., De Groot, R.J.(2012) PLoS Pathog 8: 02492
- PubMed: 22291594
- DOI: https://doi.org/10.1371/journal.ppat.1002492
- Primary Citation of Related Structures:
4C7L, 4C7W - PubMed 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.
Organizational Affiliation:
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
