Mechanism of Action of Choleragen: Effect of Toxin on Binding of Guanyl Nucleotides

Abstract

Choleragen (cholera toxin), the enterotoxin produced by Vibrio cholerae which is in large part responsible for the symptomatology of cholera, exerts its effects on cells through the activation of adenylate cyclase, resulting in an increase in intracellular cAMP(1–3). Adenylate cyclase, a membrane-bound, multisubunit system, consists of at least three components: a specific hormone receptor, a guanyl nucleotide-binding protein referred to as G/F, and a catalytic unit(4, 5). The hormone receptors are necessary for the binding of specific agonists to the cell membrane and are responsible, for example, for the effect of certain prostaglandins and peptide hormones on intracellular cAMP(4); the catalytic unit is responsible for the conversion of ATP to cAMP(6, 7), and G/F is necessary for the coupling of receptor and catalytic unit as well as for the activation of catalytic unit by guanyl nucleotides(4, 5).