Model for ExoY–F-actin interaction. ExoY is inactive in the absence of activator, F-actin, possibly because of a highly flexible catalytic center. Activation of the toxin by F-actin may occur in two steps. First, the C terminus of ExoY interacts with F-actin in proximity to the Asp-25 residue of an actin molecule. Second, a second interaction of the ExoY catalytic core with an adjacent actin molecule on the filament may trigger conformational changes of ExoY, resulting in the reorganization of its catalytic site and stimulation of enzymatic activity.