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. Author Summary Glycans cover the surface of every living cell. In vertebrates, these sugar trees commonly terminate with sialic acid (Sia) and, in consequence, Sias have become the attachment factors of choice for a multitude of pathogens: protozoa, bacteria and viruses alike. To ensure selectivity, viruses evolved to target distinct Sia species. Whether a particular type of Sia serves as receptor may depend -amongst others- on the absence or presence of specific Sia modifications. For example, most group A betacoronaviruses attach to 9- O -acetylated Sias. However, some murine coronaviruses have switched to using 4- O -acetylated Sias instead. In chemical/molecular terms this represents a momentous shift in receptor usage. We now have crystallized the hemagglutinin-esterase protein (HE) of a murine coronavirus and have solved the structure of its sugar-binding domain. Our findings reveal in exquisite detail the interactions between Sia binding site and cognate receptor. The data allow a reconstruction of how, during coronavirus evolution, the switch in receptor usage may have come about.
【초록키워드】 Evolution, Coronaviruses, coronavirus, Pathogenesis, binding site, Hemagglutinin-esterase, Protein, specificity, Lineage, Bacteria, cell tropism, glycoprotein, receptor, MHV, change, glycan, binding, Ligand, Interaction, Protozoa, sugar, sialic acid, Major, mouse hepatitis virus, Factor, domains, Author, complex, domain, shift, modifications, virion, architecture, organ, vertebrates, Topology, MOST, murine, consequence, virus, example, coronavirus, changes in, absence, changed, resolved, living cell, betacoronavirus,