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

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. © 2012 langereis et al.