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Cholera toxin increases cAMP levels by
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- modifying Gi protein
- modifying Gs protein
- binding to adenylate cyclase
- activating cAMP phosphodiesterase
Correct Option: B
Cholera toxin is produced by the CTXf bacteriophage residing within the bacteria. Cholera toxin consists of an A subunit coupled to a B subunit: the A subunit consists of an A1 domain containing the enzymatic active site, and an A2 domain that has an a-helical tail, while the B subunit contains five identical peptides that assemble into a pentameric ring surrounding a central pore. The A and B subunits of cholera toxin are produced in the cytosol by two genes that overlap by one base, and are then assembled into a toxin in the periplasm located between the inner membrane and the outer cell wall of the bacteria. 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 A/B cholera toxin must undergo cleavage of the A1 domain from the A2 domain in order for A1 to become an active enzyme. Once inside the enterocyte, the enzymatic A1 fragment of the toxin A subunit enters the cytosol, where it activates the G protein GS? 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 diarrhea.