Effects of bilayer composition and physical properties on the phospholipase C and sphingomyelinase activities of Clostridium perfringens α-toxin

► α-Toxin, a major determinant of Clostridium perfringens toxicity, exhibits both phospholipase C and sphingomyelinase activities. ► Both activities are enhanced by cholesterol and by phospholipids with intrinsic negative curvatures, and inhibited by lipids with positive intrinsic curvatures. ► Phospholipids with a net negative charge in the headgroup do not exert any marked effects on the lipase activities. ► Sphingomyelinase activity decreases with increasing vesicle diameter, while phospholipase C activity increases with increasing vesicle size. ► The two lipase activities in the toxin appear to have distinct, but partially overlapping and interacting active sites.