Association of polyalanine and polyglutamine coiled coils mediates expansion disease-related protein aggregation and dysfunction.

ABSTRACT: The expansion of homopolymeric glutamine (polyQ) or alanine (polyA) repeats in certain proteins owing to genetic mutations induces protein aggregation and toxicity, causing at least 18 human diseases. PolyQ and polyA repeats can also associate in the same proteins, but the general extent of their association in proteomes is unknown. Furthermore, the structural mechanisms by which their expansion causes disease are not well understood, and these repeats are generally thought to misfold upon expansion into aggregation-prone β-sheet structures like amyloids. However, recent evidence indicates a critical role for coiled-coil (CC) structures in triggering aggregation and toxicity of polyQ-expanded proteins, raising the possibility that polyA repeats may as well form these structures, by themsel

SUBMITTER: Pelassa I 

PROVIDER: S-EPMC4049302 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature