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The 2.2-Angstrom resolution crystal structure of the carboxy-terminal region of ataxin-3.

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 ?-helical conformations in the crystal structure. The polyQ sequence in ?-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 ?-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.

SUBMITTER: Zhemkov VA

PROVIDER: S-EPMC4794786 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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The 2.2-Angstrom resolution crystal structure of the carboxy-terminal region of ataxin-3.

Zhemkov Vladimir A VA Kulminskaya Anna A AA Bezprozvanny Ilya B IB Kim Meewhi M

FEBS open bio 20160218 3

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 ...[more]

PMID: 27047745

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