Impact of Guanidine Hydrochloride on the shapes of Prothymosin-α and α-Synuclein is dramatically different

The effects of Guanidine Hydrochloride (GdmCl) on two Intrinsically Disordered Proteins (IDPs) are investigated using simulations of the Self-Organized Polymer-IDP (SOP-IDP) model. The impact of GdmCl is taken into account using the Molecular Transfer Model(MTM). We show that, due to dramatic reduction in the stiffness of the highly charged Prothymosin- (ProT) with increasing concentration of GdmCl ([GdmCl]), the radius of gyration (Rg) decreases sharply till about 1.0M. Above 1.0M, ProT expands, caused by the swelling effect of GdmCl. In contrast, Rg of -Synuclein (Syn) swells as continuously as [GdmCl] increases, with most of the expansion occurring at concentrations less than 0.2M. Strikingly, the amplitude of the Small Angle X-ray Scattering (SAXS) profiles for ProT increases till [GdmCl]{approx} 1.0M and decreases beyond 1.0M. The [GdmCl]-dependent SAXS profiles for Syn, which has a pronounced bump at small wave vector (q [~] 0.5nm-1) at low [GdmCl] ([≤] 0.2M), monotonically decrease at all values of [GdmCl]. The contrasting behavior predicted by the combination of MTM and SOP-IDP simulations may be qualitatively understood by modeling ProT as a strongly charged polyelectrolyte with nearly uniform density of charges along the chain contour and Syn as a nearly neutral polymer, except near the C-terminus where the uncompensated negatively charged residues are located. The precise predictions for the SAXS profiles as a function of [GdmCl] can be readily tested.