Evolutionary model of repeat insertions in Ataxin-3 traces the origin of the polyglutamine stretch to an ancestral ubiquitin binding module.

ABSTRACT: The human ataxin-3 protein contains an N-terminal Josephin domain, composed of a papain-like cysteine protease with a helical hairpin insertion, and a C-terminal region with two or three ubiquitin interacting motifs and a polyglutamine tract. Expansion of the polyglutamine tract leading to protein aggregation and neuronal degradation has been linked to Machado-Joseph disease/spinocerebellar ataxia type 3, the most common form of dominantly inherited ataxia. In this study, we performed sequence self-homology dot plot analysis and compared orthologous proteins to analyze the architecture of ataxin-3 during the evolution of Filozoa. This analysis uncovered up to three additional repetitions of the ubiquitin binding motif in ataxin-3, including the helical hairpin insertion in the Josephin dom

SUBMITTER: Felicio D 

PROVIDER: S-EPMC11590126 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature