The Interaction of Cofilin with the Actin Filament

Cofilin is a key actin-binding protein that is critical for controlling the assembly of actin within the cell. Here, we present the results of molecular docking and dynamics studies using a muscle actin filament and human cofilin I. Guided by extensive mutagenesis results and other biophysical and structural studies, we arrive at a model for cofilin bound to the actin filament. This predicted structure agrees very well with electron microscopy results for cofilin-decorated filaments, provides molecular insight into how the known F- and G-actin sites on cofilin interact with the filament, and also suggests new interaction sites that may play a role in cofilin binding. The resulting atomic-scale model also helps us understand the molecular function and regulation of cofilin and provides testable data for future experimental and simulation work.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (265 K)Download as PowerPoint slideHighlights► We construct an atomic model for the F-actin/cofilin complex. ► Resultant structure matches most known mutations and agrees with structural data. ► New amino acids that may be important to binding were identified.