Given what we know about the mechanistic target of cholera t

Given what we know about the mechanistic target of cholera toxin and pertussis toxin (Cholera inhibits the GTPase activity of Galpha and Pertussis inactivates the Galpha subunit Describe the effects of cholera toxin on the activity of the GPCR that it targets. What about Pertussis Toxin?

Solution

Mechanistic target of cholera toxin:

Cholera toxin is a protein complex, made up of six protein subunits: a single copy of the A subunit and five copies of the B subunit, secreted by bacterium Vibrio cholerae. When cholera toxin is released from the bacteria in the infected intestine, it binds to the intestinal cells known as enterocytes through the interaction of the pentameric B subunit of the toxin with the GM1 ganglioside receptor on the intestinal cell, triggering endocytosis of the toxin. Next the subunit A of cholera toxin proteolytically activated and enter the cytosol. Then it activates the G protein, G_s through an ADP-ribosylation reaction that acts to lock the G protein in its GTP-bound form, thereby continually stimulating adenylate cyclase to produce cAMP.  The high cAMP levels activate the cystic fibrosis transmembrane conductance regulator (CFTR), causing a dramatic efflux of ions and water from infected enterocytes, leading to watery diarrhoea.

Mechanistic action of pertusis toxin:

Pertusis toxin (PT) is a exotoxin, produced by the bacterium Bordetella pertussis, having two sub units; subunit A possesses enzyme activity and subunit B has transport activity. Initially PT is in inactive form. Following PT binding to a cell membrane receptor, it is taken up in an endosome, after which it undergoes retrograde transport to the trans-Golgi network and endoplasmic reticulum. At some point during this transport, the A subunit becomes activated which catalyzes the ADP-ribosylation of the _i subunits of the heterotrimeric G protein. This prevents the G proteins from interacting with G protein-coupled receptors (GPCRs) on the cell membrane, thus interfering with intracellular communication. The Gi subunits remain locked in their GDP-bound, inactive state, thus unable to inhibit adenylate cyclase activity, leading to increased cellular concentrations of cAMP. Increased intracellular cAMP affects normal biological signaling.