Protofilament Structure and Supramolecular Polymorphism of Aggregated Mutant Huntingtin Exon 1.

ABSTRACT: Huntington's disease is a progressive neurodegenerative disease caused by expansion of the polyglutamine domain in the first exon of huntingtin (HttEx1). The extent of expansion correlates with disease progression and formation of amyloid-like protein deposits within the brain. The latter display polymorphism at the microscopic level, both in cerebral tissue and in vitro. Such polymorphism can dramatically influence cytotoxicity, leading to much interest in the conditions and mechanisms that dictate the formation of polymorphs. We examine conditions that govern HttEx1 polymorphism in vitro, including concentration and the role of the non-polyglutamine flanking domains. Using electron microscopy, we observe polymorphs that differ in width and tendency for higher-order bundling. Strikingly,

SUBMITTER: Boatz JC 

PROVIDER: S-EPMC8170701 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature