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-domain protein. Using truncated forms of alpha-toxin the phospholipase C active site was shown to be located in the amino-terminal domain. Crystallographic studies have confirmed this organisation and have also revealed that the carboxy-terminal domain is structurally similar to the phospholipid-binding domains in eukaryotic proteins. This information has been used to devise a model predicting how alpha-toxin interacts with membranes via calcium-mediated recognition of phospholipid head groups and the interaction of hydrophobic amino acids with the phospholipid tail group. The binding of alpha-toxin to membranes appears to result in the opening of the active site allowing hydrolysis of membrane phospholipids.
Titball
R W
RW
Defence Evaluation and Research Agency, CBD Porton Down, Salisbury, Wilts, UK. rtitball@dera.gov.uk
Naylor
C E
CE
Miller
J
J
Moss
D S
DS
Basak
A K
AK
D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D001665:Binding Sites; D002135:Calcium-Binding Proteins; D002462:Cell Membrane / Q000378:metabolism; D003016:Clostridium perfringens / Q000472:pathogenicity*; D003460:Crystallization; D006801:Humans; D011487:Protein Conformation; D010738:Type C Phospholipases / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity
D001427:Bacterial Toxins; D002135:Calcium-Binding Proteins; D010738:Type C Phospholipases; C040649:alpha toxin, Clostridium perfringens