The 2.2‐Angstrom resolution crystal structure of the carboxy‐terminal region of ataxin‐3. Issue 3 (18th February 2016)

• Record Type: Journal Article
• Authors: Zhemkov, Vladimir A.; Kulminskaya, Anna A.; Bezprozvanny, Ilya B.; Kim, Meewhi
• Is Part Of: FEBS open bio. Volume 6:Issue 3(2016)
• Page Start: 168
• Page End: 178
• Publication Date: 2016-02-18
• Subjects: ataxia -- ataxins -- Huntington's disease -- polyglutamine -- triplet repeat disorder; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.12029
• Languages: English
• ISSNs: 2211-5463

Abstract

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.