Experimental Polyproline II Propensities Describe Sequence-Dependent Variability in the Hydrodynamic Size of Intrinsically Disordered Proteins

Abstract

The properties of disordered proteins are thought to depend on intrinsic conformational propensities for polyproline II (PPII) structure. While intrinsic PPII propensities have been measured for the common biological amino acids in short peptides, the ability of these experimentally determined propensities to quantitatively reproduce structural behavior in intrinsically disordered proteins (IDPs) has not been established. Presented here are results from molecular simulations of disordered proteins showing that the hydrodynamic radius (Rh) can be predicted from experimental PPII propensities with good agreement. The simulations demonstrate that Rh and chain propensity for PPII structure are linked via a simple power-law scaling relationship, which was tested using the experimental Rh of 22 IDPs covering a wide range of peptide lengths, net charge, and sequence composition. The relationship between Rh and PPII structure was also tested by glycine substitutions applied to a prototypical IDP to demonstrate a method for measuring PPII propensities in disordered proteins. Overall, the results from these studies indicate that the hydrodynamic dimensions of IDPs are evidence of considerable sequence-dependent backbone propensities for PPII structure that qualitatively, if not quantitatively, match conformational propensities measured in peptides.