Crystal structure of the multifunctional paramyxovirus hemagglutinin-neuraminidase

Paramyxoviruses are the main cause of respiratory disease in children. One of two viral surface glycoproteins, the hemagglutinin-neuraminidase (HN), h as several functions in addition to being the major surface antigen that in duces neutralizing antibodies. Here we present the crystal structures of Ne wcastle disease virus HN alone and in complex with either an inhibitor or w ith the beta -anomer of sia(ic acid. The inhibitor complex reveals a typica l neuraminidase active site within a beta -propeller fold. Comparison of th e structures of the two complexes reveal differences in the active site, su ggesting that the catalytic site is activated by a conformational switch. T his site may provide both sialic acid binding and hydrolysis functions sinc e there is no evidence for a second sialic acid binding site in HN. Evidenc e for a single site with dual functions is examined and supported by mutage nesis studies. The structure provides the basis for the structure-based des ign of inhibitors for a range of paramyxovirus-induced diseases.