Pertussis Toxin-ATP Complex: Difference between revisions

Following the pertussis toxin binding to the cell membrane (B subunit binds to terminal sialic acid residues), the toxin is taken up by an endosome and transported from the plasma membrane via the Golgi apparatus to the endoplasmic reticulum (ER) where finally membrane translocation occurs.  The destabilization of PT occurs in the ER prior to membrane translocation.  After binding of ATP, cleavage of the single disulphide bond by protein disulphide isomerase (PDI) occurs in subunit S1 <scene name='Pertussis_Toxin-ATP_Complex/Disulphide_bonds_breaking/1'>(Cys 41-Cys 201)</scene> and is believed to trigger a conformational change necessary to expose the active site to its substrates. The reducation step takes place after interaction of PT with ATP.  After destabilization, the S1 becomes active and catalyzes the ADP-ribosylation of the alpa-subunit of regulatory trimeric G-proteins (Giα).  This then prevents Giα from inhibiting adenylate cyclase and leads to an increase in intracellular levels of cyclic AMP (cAMP).  The increase in cAMP affects normal biological signaling and causes severe effects such as hypoglycemia.