The molecular basis of the self/nonself selectivity of a coelenterate toxin.

Coelenterates produce potent hemolysins inhibited by sphingomyelin (SM). Remarkably, instead of this lipid, their membranes contain a phosphono analogue of it. Using coelenterolysin (CL), a toxin produced by the sea anemone Phymactis clematis, we have examined a possible connection between these two peculiar traits. Our experiments showed that, while SM binds this lysin and inhibits its hemolytic activity, the endogenous PnSL do neither. In addition, liposomes made of bovine erythrocyte lipids are rapidly disrupted by CL, while those made of P. clematis lipids are completely resistant to it. However, if small amounts of SM are added to the P. clematis lipids, the resulting liposomes become sensitive to CL. Taken together, our results show for the first time that substitution of SM by its phosphono analogue is the molecular basis for the selectivity of an anthozoan toxin. We therefore propose that exotoxin production and membrane composition are coadapted traits that confer on the coelenterates a significant evolutionary advantage.