NAD-glycohydrolase activity of botulinum C2 toxin: a possible role of component I in the mode of action of the toxin.
C2 toxin (C2T) elaborated by Clostridium botulinum types C and D is composed of two separate protein components, designated components I and II, which individually have little activity, but, when mixed and treated with trypsin, exert the potent activity. The present study provides the evidence that component I of the toxin catalyzes the hydrolysis of NAD into nicotinamide and ADP-ribose, whereas component II does not, indicating that component I of C2T has NAD-glycohydrolase activity, which ability is shared with cholera and diphtheria toxins. However, C2T affected neither glycerol production of fat cells nor protein synthesis in cell-free system. Component I of C2T in the presence of [alpha-32P]NAD radiolabeled a protein of Mr 46,000 in the supernatant fractions of mouse tissue homogenates; the protein was abundant in brain, lung and intestine, whereas there was little or none of the protein in muscle. These results indicate that component I can catalyze the covalent attachment of the ADP-ribose moiety of NAD to intracellular protein, which differs from those modified with cholera and diphtheria toxins. The present data, together with previous findings, suggest that the biological activity of C2T is elicited by ADP-ribosylation activity of component I, which is internalized into the cells after binding to the receptor site introduced with the binding of component II to the cell surface membrane.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001905:Botulinum Toxins / Q000378:metabolism*; D005990:Glycerol / Q000096:biosynthesis; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D009244:NAD+ Nucleosidase / Q000378:metabolism*; D014176:Protein Biosynthesis
D046911:Macromolecular Substances; D000246:Adenosine Diphosphate Ribose; D009244:NAD+ Nucleosidase; D001905:Botulinum Toxins; D005990:Glycerol