Abstract
An expansion of polyglutamine (polyQ) sequence in ataxin-3 protein causes spinocerebellar ataxia type 3, an inherited neurodegenerative disorder. The crystal structure of the polyQ-containing carboxy-terminal fragment of human ataxin-3 was solved at 2.2-Å resolution. The Atxn3 carboxy-terminal fragment including 14 glutamine residues adopts both random coil and α-helical conformations in the crystal structure. The polyQ sequence in α-helical structure is stabilized by intrahelical hydrogen bonds mediated by glutamine side chains. The intrahelical hydrogen-bond interactions between glutamine side chains along the axis of the polyQ α-helix stabilize the secondary structure. Analysis of this structure furthers our understanding of the polyQ-structural characteristics that likely underlie the pathogenesis of polyQ-expansion disorders.