Cholera toxin (also known as choleragen and sometimes abbreviated to CTX, Ctx or CT) is an AB5 multimeric protein complex secreted by the bacterium Vibrio cholerae. CTX is responsible for the massive, watery diarrhea characteristic of cholera infection. It is a member of the heat-labile enterotoxin family. History Cholera toxin was discovered in 1959 by Indian microbiologist Sambhu Nath De. Structure The complete toxin is a hexamer made up of a single copy of the A subunit (part A, enzymatic, ), and five copies of the B subunit (part B, receptor binding, ), denoted as AB5. Subunit B binds while subunit A activates the G protein which activates adenylate cyclase. The three-dimensional structure of the toxin was determined using X-ray crystallography by Zhang et al. in 1995. The five B subunits—each weighing 11 kDa, form a five-membered ring. The A subunit which is 28 kDa, has two important segments. The A1 portion of the chain (CTA1) is a globular enzyme payload that ADP-ribosylates G proteins, while the A2 chain (CTA2) forms an extended alpha helix which sits snugly in the central pore of the B subunit ring. This structure is similar in shape, mechanism, and sequence to the heat-labile enterotoxin secreted by some strains of the Escherichia coli bacterium. Pathogenesis Cholera toxin acts by the following mechanism: First, the B subunit ring of the cholera toxin binds to GM1 gangliosides on the surface of target cells. If a cell lacks GM1, the toxin most likely binds to other types of glycans, such as Lewis Y and Lewis X, attached to proteins instead of lipids. Once bound, the entire toxin complex is endocytosed by the cell and the reduction of a disulfide bridge releases the cholera toxin A1 (CTA1) chain. The endosome is moved to the Golgi apparatus, where the A1 protein is recognized by the endoplasmic reticulum (ER) chaperone, protein disulfide isomerase. The A1 chain is then unfolded and delivered to the membrane, where Ero1 triggers the release of the A1 protein by oxidation of protein disulfide isomerase complex. As the A1 protein moves from the ER into the cytoplasm by the Sec61 channel, it refolds and avoids deactivation as a result of ubiquitination. CTA1 is then free to bind with a human partner protein called ARF6 (ADP-ribosylation factor 6); binding to Arf6 drives a change in the shape of CTA1 which exposes its active site and enables its catalytic