Coupled folding and binding kinetics in the intrinsically disordered peptide IA$_{3}$*

IA$_{3}$ is an intrinsically disordered 68 residue peptide and is an endogenous inhibitor of yeast proteinase A (YPrA). X-ray crystallography of the IA$_{3}\cdot $YPrA complex [Li et al, Nat. Struct. Biol. (7), 113-117 (2000)] indicates that the N-terminus of IA$_{3}$ adopts an alpha-helical fold when it is bound to the YPrA active site. We have used equilibrium circular dichroism and multi-wavelength, nanosecond time-resolved laser temperature-jump spectroscopy to study the coupled folding and binding interaction of IA$_{3}$ with YPrA. Our initial measurements of the rate of helix formation in free IA$_{3}$ indicate mono-exponential folding kinetics that extrapolate to k$_{F} \sim $ 10$^{5}$/s at room temperature in aqueous solutions. By comparing this rate to the kinetics we observe for IA$_{3}$ interacting with YPrA, we can assess possible mechanisms for the coupled folding and binding of IA$_{3}$.