Abrogation of prenucleation, transient oligomerization of the Huntingtin exon 1 protein by human profilin I.

ABSTRACT: Human profilin I reduces aggregation and concomitant toxicity of the polyglutamine-containing N-terminal region of the huntingtin protein encoded by exon 1 (htt^ex1) and responsible for Huntington's disease. Here, we investigate the interaction of profilin with htt^ex1 using NMR techniques designed to quantitatively analyze the kinetics and equilibria of chemical exchange at atomic resolution, including relaxation dispersion, exchange-induced shifts, and lifetime line broadening. We first show that the presence of two polyproline tracts in htt^ex1, absent from a shorter huntingtin variant studied previously, modulates the kinetics of the transient branched oligomerization pathway that precedes nucleation, resulting in an increase in the populations of the on-p

SUBMITTER: Ceccon A 

PROVIDER: S-EPMC7084121 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature