The Kinetics of Cooperative Cofilin Binding to Actin Filaments

Abstract

The interaction of cofilin with actin filaments displays positive cooperativity. The equilibrium binding and associated thermodynamic parameters of this interaction are well described by a simplified, one-dimensional Ising model with nearest neighbor interactions [De La Cruz (2005) J. Mol. Biol. 346, 557-564]. Here we evaluate the ability of the model to account for cooperative association kinetics and to determine the kinetic contributions to cooperative binding. A Monte Carlo based simulation protocol that allows for nearest-neighbor interactions between adjacent binding sites was employed to globally fit time courses of cofilin binding. A consistent set of binding parameters in good agreement with the equilibrium thermodynamic parameters describes well the experimental data across a wide range of cofilin concentrations. We conclude that despite its simplicity, the one-dimensional Ising model with nearest neighbor cooperative interactions, is a reliable model for analyzing and interpreting the thermodynamics and kinetics of cooperative cofilin-actin filament interactions. The methods developed for this system will be applicable to the kinetics analysis of cooperative ligand binding to linear biological polymers.