Solvent-induced collapse of alpha-synuclein and acid-denatured cytochrome c

The effects of solution conditions on protein collapse were studied by meas uring the hydrodynamic radii of two unfolded proteins, alpha -synuclein and acid-denatured ferricytochrome c, in dilute solution and in 1 M glucose. T he radius of alpha -synuclein in dilute solution is less than that predicte d for a highly denatured state, and adding 1 M glucose causes further colla pse. Circular dichroic data show that alpha -synuclein lacks organized stru cture in both dilute solution and 1 M glucose. On the other hand, the radiu s of acid-denatured cytochrome c in dilute solution is consistent with that of a highly denatured state, and 1 M glucose induces collapse to the size and structure of native cytochrome c. Taken together, these data show that alpha -synuclein, a natively unfolded protein. is collapsed even in dilute solution, but lacks structure.