How a Highly Acidic SH3 Domain Binds to Its Intrinsically Disordered Partner through the Formation of an Encounter Complex Intermediate

However, the role of long-range electrostatic interactions in intrinsically disordered protein (IDP) binding is less clear, as they often bind in multiple steps, including initial formation of a disordered encounter complex, followed by rearrangement into the bound state. We varied the salt concentration to probe the role of long-range electrostatic interactions in the binding of the highly charged AbpSH3 domain and the oppositely charged IDP ArkA.

Using isothermal titration calorimetry, we observed that salt enthalpically destabilizes the bound complex. Molecular dynamics and NMR experiments revealed that salt has little effect on the bound state structure. However, simulations show that salt destabilizes the encounter complex intermediate, which primarily affects the association rate as measured by NMR.