Opening of the active site of Clostridium perfringens alpha-toxin may be triggered by membrane binding

On the basis of amino acid sequence homologies with other phospholipases C, the alpha -toxin of Clostridium perfringens was predicted to be a two-doma in protein. Using truncated forms of alpha -toxin the phospholipase C activ e site was Shown to be located in the amino-terminal domain. Crystallograph ic studies have confirmed this organisation and have also revealed that the carboxy-terminal domain is structurally similar to the phospholipid-bindin g domains in eukaryotic proteins. This information has been used to devise a model predicting how alpha -toxin interacts with membranes via calcium-me diated recognition of phospholipid head groups and the interaction of hydro phobic amino acids with the phospholipid tail group. The binding of a-toxin to membranes appears to result in the opening of the active site allowing hydrolysis of membrane phospholipids.