Huntingtin exon 1 fibrils feature an interdigitated β-hairpin-based polyglutamine core.

ABSTRACT: Polyglutamine expansion within the exon1 of huntingtin leads to protein misfolding, aggregation, and cytotoxicity in Huntington's disease. This incurable neurodegenerative disease is the most prevalent member of a family of CAG repeat expansion disorders. Although mature exon1 fibrils are viable candidates for the toxic species, their molecular structure and how they form have remained poorly understood. Using advanced magic angle spinning solid-state NMR, we directly probe the structure of the rigid core that is at the heart of huntingtin exon1 fibrils and other polyglutamine aggregates, via measurements of long-range intramolecular and intermolecular contacts, backbone and side-chain torsion angles, relaxation measurements, and calculations of chemical shifts. These experiments reveal th

SUBMITTER: Hoop CL 

PROVIDER: S-EPMC4760812 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature