Mapping the self-association domains of ataxin-1: identification of novel non overlapping motifs.

Abstract

The neurodegenerative disease spinocerebellar ataxia type 1 (SCA1) is caused by aggregation and misfolding of the ataxin-1 protein. While the pathology correlates with mutations that lead to expansion of a polyglutamine tract in the protein, other regions contribute to the aggregation process as also non-expanded ataxin-1 is intrinsically aggregation-prone and forms nuclear foci in cell. Here, we have used a combined approach based on FRET analysis, confocal microscopy and in vitro techniques to map aggregation-prone regions other than polyglutamine and to establish the importance of dimerization in self-association/foci formation. Identification of aggregation-prone regions other than polyglutamine could greatly help the development of SCA1 treatment more specific than that based on targeting the low complexity polyglutamine region.

• Authors: Rajesh P Menon, Daniel Soong, Cesira de Chiara, Mark Holt, John E McCormick, Narayana Anilkumar, Annalisa Pastore
• Journal: PeerJ (PeerJ) Vol. 2 Pg. e323 ( 2014) ISSN: 2167-8359 [Print] United States
• PMID: 24711972 (Publication Type: Journal Article)