title: Identification of a self-association region within the SCA1 gene product, ataxin-1.
abstract: Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by the expansion of a polyglutamine tract within the SCA1 gene product, ataxin-1. Expansion of this tract is believed to result in a gain of function by the mutant protein, perhaps through altered self-associations or interactions with other cellular proteins. We have used the yeast two hybrid system to determine if ataxin-1 is capable of multimerization. This analysis revealed that ataxin-1 does have the ability to self-associate, however, this association does not appear to be influenced by expansion of the polyglutamine tract. Consistent with this finding, deletion analysis excluded the involvement of the polyglutamine tract in ataxin-1 self-association, and instead localized the multimerization region to amino acids 495-605 of the wild type protein. These results, while identifying an ataxin-1 self-interaction region, fail to support a proposed model of polar-zipper mediated multimerization involving the ataxin-1 polyglutamine tract.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455, USA.
authors.forename: E N
authors.initials: EN
authors.lastname: Burright
authors.forename: J D
authors.initials: JD
authors.lastname: Davidson
authors.forename: L A
authors.initials: LA
authors.lastname: Duvick
authors.forename: B
authors.initials: B
authors.lastname: Koshy
authors.forename: H Y
authors.initials: HY
authors.lastname: Zoghbi
authors.forename: H T
authors.initials: HT
authors.lastname: Orr
mesh_terms: D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D003001:Cloning, Molecular; D017931:DNA Primers; D015723:Gene Library; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D014170:Transformation, Genetic; D015003:Yeasts; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; C097188:polyglutamine; D001616:beta-Galactosidase