Formation and Structure of Wild Type Huntingtin Exon-1 Fibrils.

ABSTRACT: The fact that the heritable neurodegenerative disorder Huntington's disease (HD) is autosomal dominant means that there is one wild type and one mutant allele in most HD patients. The CAG repeat expansion in the exon 1 of the protein huntingtin (HTT_ex1) that causes the disease leads to the formation of HTT fibrils in vitro and vivo. An important question for understanding the molecular mechanism of HD is which role wild type HTT plays for the formation, propagation, and structure of these HTT fibrils. Here we report that fibrils of mutant HTT_ex1 are able to seed the aggregation of wild type HTT_ex1 into amyloid fibrils, which in turn can seed the fibril formation of mutant HTT_ex1. Solid-state NMR and electron paramagnetic resonance data showed tha

SUBMITTER: Isas JM 

PROVIDER: S-EPMC5575822 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature