Polyglutamine repeats are a halmark of several neurodegenerative diseases, most notably Huntington's disease.  These sequences cause aggregation which likely leads to cell death.  By measuring intramolecular contact formation of polyglutamine peptides of various lengths, we found the reaction-limited rates, k_R, did not decrease rapidly with length.  The length dependence could be modeled with a wormlike chain with a persistence length of 13.5 Ǻ, much longer than the ~ 4 Ǻ found for other peptides and unfolded proteins.  This suggests that aggregation results from an extended conformation that is more likely in polyglutamine.

By measuring the folding rates with different probes (tryptophan fluorescence intensity (left panel), spectral shift (top panel) and lifetime) and by different folding methods (rapid mixing and laser T-jump (by the Gruebele group)) we see different dynamics for different probes (bottom middle panel).  The observed rates can be modeled as diffusion on a 1-dimensional landscape that responds to the different probes at different locations (bottom right panel).  At the lowest temperatures measured there is no barrier between the folded and unfolded states so the protein proceeds to fold by moving "downhill" on the landscape.