Conformational Properties of Unfolded HypF-N

We have measured the intramolecuolar diffusion rate between distant residues in the aggregation-prone protein HypF-N under various denaturing conditions, Using the method of cysteine quenching of the tryptophan triplet state, we find that intramolecular diffusion remains roughly constant at high concentrations of denaturant (2-6 M GdnHCl) and slows down at low concentrations of denaturant, but the decrease is not uniform throughout the chain. Extrapolation of these measurements to 0 M GdnHCl gives D similar to 10(-7) cm(2) s(-1), about I order of magnitude lower than unstructured peptides and at least 2 orders of magnitude higher than well-behaved proteins. This suggests that there is it dynamic range of conformational reorganization within which partially Unfolded states are prone to aggregation.