The Cholera Toxin

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 (for more on G-proteins, see the Molecule of the Month for March 2004 ). 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.

 

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.