The A protomer of islet-activating protein, pertussis toxin, as an active peptide catalyzing ADP-ribosylation of a membrane protein

Arch Biochem Biophys. 1983 Jul 1;224(1):290-8. doi: 10.1016/0003-9861(83)90212-6.


Islet-activating protein (IAP), pertussis toxin, is an oligomeric protein composed of as A protomer and a B oligomer. IAP and its A protomer were equipotent, on a molar basis, in enhancing GTP-dependent adenylate cyclase activity and in causing ADP-ribosylation of the 41,000 Mr protein when directly added to the cell-free membrane preparation from rat C6 glioma cells. Similar actions of IAP observed upon its addition to intact C6 cells were not mimicked by its A protomer, indicating that the A protomer had to be associated with the B oligomer to become accessible to its site of action on the inner surface of the membrane of intact cells. The A protomer, but not IAP, exhibited NAD-glycohydrolase activity in the reaction mixture lacking cellular components but containing dithiothreitol. Their actions on membranes were not accelerated by dithiothreitol, but markedly suppressed by oxidized glutathione. Thus, C6 cell membranes may possess certain "processing" enzyme(s) responsible for releasing the A protomer from the IAP molecule and for reductive cleavage of an intrachain disulfide bond in the released protomer, thereby producing an active peptide which functions to cause ADP-ribosylation of one of the subunits of guanine nucleotide regulatory protein in the receptor-adenylate cyclase system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism*
  • Adenylate Cyclase Toxin
  • Adenylyl Cyclases / metabolism
  • Animals
  • Bacterial Proteins / pharmacology*
  • Catalysis
  • Membrane Proteins / metabolism*
  • NAD / metabolism
  • Nucleoside Diphosphate Sugars / metabolism*
  • Peptide Fragments / pharmacology*
  • Pertussis Toxin
  • Rats
  • Virulence Factors, Bordetella


  • Adenylate Cyclase Toxin
  • Bacterial Proteins
  • Membrane Proteins
  • Nucleoside Diphosphate Sugars
  • Peptide Fragments
  • Virulence Factors, Bordetella
  • NAD
  • Adenosine Diphosphate Ribose
  • Pertussis Toxin
  • Adenylyl Cyclases