Lipid headgroups alter huntingtin aggregation on membranes.

ABSTRACT: Huntington's Disease is a fatal neurodegenerative disorder caused by expansion of a glutamine repeat region (polyQ) beyond a critical threshold within exon1 of the huntingtin protein (htt). As a consequence of polyQ expansion, htt associates into a variety of aggregate species that are thought to underlie cellular toxicity. Within cells, htt associates with numerous membranous organelles and surfaces that exert influence on the aggregation process. In particular, the first 17 amino acids at the N-terminus of htt (Nt17) serve as a lipid-binding domain that is intrinsically disordered in bulk solution but adopts an amphipathic α-helical structure upon binding membranes. Beyond this, Nt17 is implicated in initiating htt fibrillization. As the interaction between Nt17 and lipid membranes is li

SUBMITTER: Beasley M 

PROVIDER: S-EPMC7742038 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature