Chemical Targeting of the ATXN1 aa99-163 Interaction Site Suppresses polyQ-Expanded Protein Dimerization.

ABSTRACT: Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the expansion of a polyglutamine (polyQ) tract in the ATXN1 protein. This expansion is thought to be responsible for the gradual aggregation of the mutant protein, which is associated with increased cytotoxicity and neuronal cell death. Apart from the polyQ tract, other domains in ATXN1 are also involved in the initial events of protein aggregation, such as a dimerization domain that promotes protein oligomerization. ATXN1 interacts with various proteins; among them, MED15 significantly enhances the aggregation of the polyQ-expanded protein. Therefore, we set to identify the interaction site between ATXN1 and MED15 and assess whether its chemical targeting would affect polyQ protein aggregation. First, we predict

SUBMITTER: Gkekas I 

PROVIDER: S-EPMC12223882 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature