Toxins which activate adenylate cyclase.
Cholera toxin and other heat-labile enterotoxins have the same subunit structure (A5B) and all catalyse the mono ADP-ribosylation of Ns, a regulator of adenylate cyclase, probably at an arginine residue. They also ADP-ribosylate a variety of other membrane and soluble proteins at much slower rates. The rates differ from protein to protein but it may be that every arginine residue in every protein is ADP-ribosylated at some slow rate. A guanine nucleotide triphosphate is required for the ADP-ribosylation of the major (Ns) and minor substrates alike. It used to be thought that all the substrates were GTP-binding proteins but this cannot be so. Rather, the GTP is required because it has to bind to some additional site on the membrane, termed 'S', in a cooperative event that involves a soluble protein called cytosolic factor (CF). If we expose erythrocyte membranes to CF and the GTP analogue Gpp(NH)p we can later extract in detergent a factor or complex that confers upon naive erythrocyte membranes the ability to be ADP-ribosylated. Pertussis toxin also has an A5B structure and acts on an intracellular substrate for ADP-ribosylation, namely the negative regulator of adenylate cyclase, called Ni. ADP-ribosylation prevents the reduction of cyclase activity by inhibitory hormones. The ADP-ribosylation of Ns or Ni does not affect the rate of ADP-ribosylation of the other protein.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D004768:Enterotoxins / Q000494:pharmacology*; D004789:Enzyme Activation; D004910:Erythrocyte Membrane / Q000378:metabolism; D006150:Guanine Nucleotides / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008970:Molecular Weight; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella
D037361:Adenylate Cyclase Toxin; D001427:Bacterial Toxins; D004768:Enterotoxins; D006150:Guanine Nucleotides; D046911:Macromolecular Substances; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D002772:Cholera Toxin; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases