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Cholera toxin



 

Cholera toxin (sometimes abbreviated to CTX, Ctx, or CT) is a protein complex secreted by the bacterium Vibrio cholerae.[1] CTX is responsible for the harmful effects of cholera infection.

Additional recommended knowledge

Contents

Structure

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.[2]

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.[3]

This structure is similar in shape, mechanism, and sequence to the heat-labile enterotoxin secreted by some strains of the Escherichia coli bacterium.

Mechanism

Virulent strains of V. cholerae carry a strain of lysogenic bacteriophage called CTXf or CTXφ. It is this bacteriophage which actually carries the genes for the cholera toxin subunits.[4]

Synthesis

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.[5]

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.

Applications

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 [1].

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.

See also

  • Enterotoxin

References

  1. ^ Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology, 4th ed., McGraw Hill, p. 375. ISBN 0838585299. 
  2. ^ Zhang R, Scott D, Westbrook M, Nance S, Spangler B, Shipley G, Westbrook E (1995). "The three-dimensional crystal structure of cholera toxin". J Mol Biol 251 (4): 563-73. PMID 7658473.
  3. ^ De Haan L, Hirst TR (2004). "Cholera toxin: a paradigm for multi-functional engagement of cellular mechanisms (Review)". Mol. Membr. Biol. 21 (2): 77-92. PMID 15204437.
  4. ^ Davis B, Waldor M (2003). "Filamentous phages linked to virulence of Vibrio cholerae". Curr Opin Microbiol 6 (1): 35-42. PMID 12615217.
  5. ^ O'Neal C, Jobling M, Holmes R, Hol W (2005). "Structural basis for the activation of cholera toxin by human ARF6-GTP". Science 309 (5737): 1093-6. PMID 16099990.
 
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.
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