Heat-labile enterotoxin family
In molecular biology, the heat-labile enterotoxin family includes Escherichia coli heat-labile enterotoxin and cholera toxin secreted by Vibrio cholerae.
lt is so named because it is inactivated at high temperatures.
Mechanism
The A subunits are transported inside by the pentameric B subunits. It then acts by raising cAMP levels through ADP-ribosylation of the alpha-subunit of a Gs protein leading to the constitutive activation of adenylate cyclase. Elevated cAMP levels stimulate the activation of the CFTR channel thus stimulating secretion of chloride ions and water from the enterocyte into the gut lumen. This ionic imbalance causes watery diarrhea.In addition to its effects on chloride secretion, which involve the same steps as the effects of cholera toxin, Elt binds additional substrates: lipopolysaccharide on the surface of E. coli cells and A-type blood antigens. Studies have shown that these interactions can influence how the toxin associates with the bacterial surface and how effectively it is delivered to host cells, although their contribution may vary by strain and context.
Structure
These toxins consist of an AB5 multimer structure, in which a pentamer of B chains has a membrane-binding function and an A chain is needed for enzymatic activity. The B subunits are arranged as a doughnut-shaped pentamer, each subunit participating in ~30 hydrogen bonds and 6 salt bridges with its two neighbours.The A subunit has a less well-defined secondary structure. It predominantly interacts with the pentamer via the C-terminal A2 fragment, which runs through the charged central pore of the B subunits. A putative catalytic residue in the A1 fragment lies close to a hydrophobic region, which packs two loops together. It is thought that this region might be important for catalysis and membrane translocation.
The structural arrangement of E. coli type I and type II heat-labile enterotoxins are very similar, although they are antigenically distinct.