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The cholera toxin is an oligomeric complex made up of six protein subunits: a single copy of the A subunit, and five copies of the B subunit. Its three-dimensional structure was determined using X-ray crystallography by Zhang et al. in 1995.
The five B subunits—each weighing 12 kDa, and all coloured blue in the accompanying figure—form a five-membered ring. The A subunit has two important segments. The A1 portion of the chain (CTA1, red) is a globular enzyme payload that ADP-ribosylates G proteins, while the A2 chain (CTA2, orange) forms an extended alpha helix which seats snugly in the central pore of the B subunit ring.
Once secreted, the B subunit ring of CTX will bind to GM1 gangliosides on the surface of the host's cells. After binding takes place, the entire CTX complex is internalised by the cell and the CTA1 chain is released by the reduction of a disulfide bridge.
CTA1 is then free to bind with a human partner protein called ADP-ribosylation factor 6 (Arf6); binding to Arf6 drives a change in the conformation (the shape) of CTA1 which exposes its active site and enables its catalytic activity.
The CTA1 fragment catalyses ADP ribosylation from NAD to the regulatory component of adenylate cyclase, thereby activating it. Increased adenylate cyclase activity increases cyclic AMP (cAMP) synthesis causing massive fluid and electrolyte efflux, resulting in diarrhea.
Because the B subunit appears to be relatively non-toxic, researchers have found a number of applications for it in cell and molecular biology.
It has been used to trace neurons .
GM1 gangliosides are found in lipid rafts on the cell surface. B subunit complexes labelled with fluorescent tags or subsequently targeted with antibodies can be used to identify rafts.
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Cholera_toxin". A list of authors is available in Wikipedia.|