Cholera Toxin

Many bacterial toxins have two parts: one that finds a cell, the other that kills it

Cholora toxin, with the cell-binding subunit in blue and the toxic component in red.
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Bacteria pull no punches when they fight to protect themselves. Some bacteria build toxins so powerful that a single molecule can kill an entire cell. This is far more effective than chemical poisons like cyanide or arsenic. Chemical poisons attack important molecules one by one, so many, many molecules of cyanide are needed to kill a cell. Bacterial toxins use two strategies to make their toxins far more deadly than this.

Building a Deadly Toxin

The first strategy used to build super-deadly toxins is to use a targeting mechanism to deliver the toxin directly to the unlucky cell. Cholera toxin, shown here from PDB entry 1xtc , has a ring of five identical protein chains, colored blue here, which binds to carbohydrates on the surface of cells. This delivers the toxic part of the molecule, colored red, to the cell, where it can wreak its havoc.

The second deadly strategy is to use a toxic enzyme instead of a chemical poison. Enzymes are designed to perform their reactions over and over again, hopping from target to target and making their chemical changes. Thus, one enzyme can modify a whole cell full of molecules. Cholera uses this strategy once it gets inside cells. The toxic portion hops from molecule to molecule, disabling each one in turn, until the entire cell is killed.

Cholera Toxin in Action

The catalytic portion of cholera toxin performs a single function: it seeks out the G proteins used for cellular signaling and attaches an ADP molecule to them. This converts the G-protein into a permanently active state, so it sends a never-ending signal. This confuses the cell, and among other things, it begins to transport lots of water and sodium outwards. This floods the intestine, leading to life-threatening dehydration.

Several two-part toxins.
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Terrible Toxins

The two-part strategy employed by cholera toxin is highly effective, so much so that it is used by many different organisms that seek to protect themselves. A few examples from the PDB are shown here, with the targeting portion in blue and the toxic enzyme in red. These include E. coli enterotoxin (PDB entry 1ltb ), which looks and acts like cholera toxin and is a cause of intestinal problems when traveling. Pertussis toxin (PDB entry 1prt ), made by the bacterium that causes whooping cough, also attacks the G-protein signaling pathway. Diphtheria toxin (PDB entry 1mdt ) is synthesized as a single chain, but is then cut to form the two-part toxin when it is released. It shuts down protein synthesis in cells by attacking one of the elongation factors. Ricin (PDB entry 2aai ) is a powerful toxin made by the castor bean plant. Once it gets inside cells, it blocks protein synthesis by directly attacking ribosomes. For more information on toxins from a genomics perspective, take a look at the Protein of the Month at the European Bioinformatics Institute.

Exploring the Structure

PDB entry 1ltt shows how E. coli enterotoxin finds its target cells in the intestine. The structure includes five molecules of lactose, shown here at the bottom in spacefilling spheres, bound to the targeting portion of the toxin. The carbohydrate chains on a cell surface will bind in the same place when the toxin is attaching to a cell surface. You can also look at how the toxic portion is activated. It is composed of a long, extended portion (colored tan) that anchors the chain to the targeting part. When the toxin is activated, the little loop connecting these parts must clipped and a disulfide linkage must be broken (at the site shown by a star) to release the toxic portion (colored pink) into the cell. In this structure, the little loop is disordered, so the chain looks like it is already broken.

This picture was created with RasMol. You can explore these structures by clicking on the accession codes here and picking one of the options for 3D viewing.


  1. R.-G. Zhang, D. L. Scott, M. L. Westbrook, S. Nance, B. D. Spangler, G. G. Shipley and E. M. Westbrook. (1995) The Three-Dimensional Crystal Structure of Cholera Toxin. Journal of Molecular Biology 251, 563-573.
  2. T. K. Sixma, S. E. Pronk, K. H. Kalk, B. A. M. vanZanten, A. M. Berghuis, W. G. J. Hol. (1992) Lactose Binding to Heat-Labile Enterotoxin Revealed by X-ray Crystallography. Nature 355, 561-564.

September 2005, David Goodsell

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