Adenine nucleotides promote dissociation of pertussis toxin subunits.
Pertussis toxin is composed of an enzymatically active A subunit and a binding component (B oligomer). Both the holotoxin and the isolated A subunit have previously been shown to exhibit NAD glycohydrolase activity although the A subunit is more active on a molar basis than the holotoxin. We have investigated the mechanism by which ATP stimulates the activity of this toxin. Since dissociation of pertussis toxin subunits would result in increased NAD glycohydrolase activity, the ability of ATP to promote release of the A subunit from the B oligomer was examined. In the presence of the zwitterionic detergent 3-(3-cholamidopropyldimethyl)-1-ammonio)-propanesulfonate, concentrations of ATP as low as 1 microM promoted subunit dissociation. The concentration of ATP required for release of the A subunit was similar to that required for stimulation of NAD glycohydrolase activity. Both ATP and ADP promoted subunit dissociation and stimulated NAD glycohydrolase activity. In contrast, AMP and adenosine did not alter NAD glycohydrolase activity or affect subunit structure. The ability of ATP to decrease the affinity of the A subunit for the B oligomer may play a role in nucleotide stimulation of pertussis toxin activity.
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D002793:Cholic Acids / Q000494:pharmacology; D003570:Cytidine Triphosphate / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006160:Guanosine Triphosphate / Q000494:pharmacology; D046911:Macromolecular Substances; D008970:Molecular Weight; D009244:NAD+ Nucleosidase / Q000378:metabolism; D037342:Pertussis Toxin; D013942:Thymine Nucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000378:metabolism*
D000227:Adenine Nucleotides; D002793:Cholic Acids; D046911:Macromolecular Substances; D013942:Thymine Nucleotides; D010566:Virulence Factors, Bordetella; D003570:Cytidine Triphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D009244:NAD+ Nucleosidase; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate; C024157:thymidine 5'-triphosphate