Stable polyglutamine dimers can contain β-hairpins with interdigitated side chains-but not α-helices, β-nanotubes, β-pseudohelices, or steric zippers.

ABSTRACT: A common thread connecting nine fatal neurodegenerative protein aggregation diseases is an abnormally expanded polyglutamine tract found in the respective proteins. Although the structure of this tract in the large mature aggregates is increasingly well described, its structure in the small early aggregates remains largely unknown. As experimental evidence suggests that the most toxic species along the aggregation pathway are the small early ones, developing strategies to alleviate disease pathology calls for understanding the structure of polyglutamine peptides in the early stages of aggregation. Here, we present a criterion, grounded in available experimental data, that allows for using kinetic stability of dimers to assess whether a given polyglutamine conformer can be on the aggregatio

SUBMITTER: Miettinen MS 

PROVIDER: S-EPMC4008795 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature