Structural Dynamics of the Actin-Binding Domains in Dystrophin and Utrophin

Abstract

twisting of the filaments. In many mechanical cellular activities, such as cell movements, division, and controls of cell shape, modulation of filament stretching and twisting dynamics has been linked to regulatory actin-binding protein function. For example, mechanical stretching under tension causes structural changes in twist because of the mechanical characteristic of double helical filaments, that might prevent cofilin from binding to the actin filament. Therefore, it is important to quantitatively evaluate the stretching-twisting coupling behaviors of actin filaments for better understanding of actin dynamics. This study investigates the stretching-twisting coupling behaviors using molecular dynamics simulations. A model for the actin filament consisting of fourteen actin subunits in an ionic solvent was constructed as a minimal functional unit. To evaluate the stretching-twisting coupling behaviors, longitudinal and twisting Brownian motions of the filament were analyzed. The result demonstrated that the longitudinal and twisting motions of the filament exhibit a strong correlation, which indicate that the double-helix structure was untwisted under tensile force. The results obtained from this study contribute to the understanding of mechanochemical interactions concerning actin dynamics, showing that increased tensile force in the filament prevents actin regulatory proteins from binding to the filament.