Disordered Protein Diffusion under Crowded Conditions.

Intrinsically disordered proteins are important in signaling, regulation, and translocation. Understanding their diffusion under physiologically relevant conditions will yield insight into their functions. We used NMR to quantify the translational diffusion of a globular and a disordered protein in dilute solution and under crowded conditions. In dilute solution, the globular protein chymotrypsin inhibitor 2 (CI2, 7.4 kDa) diffuses faster than the disordered protein α-synuclein (14 kDa). Surprisingly, the opposite occurs under crowded conditions; α-synuclein diffuses faster than CI2, even though α-synuclein is larger than CI2. These data show that shape is a key parameter determining protein diffusion under crowded conditions, adding to the properties known to be affected by macromolecular crowding. The results also offer a clue about why many signaling proteins are disordered.