In molecular biology, the heat-labile enterotoxin family includes ''

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

'' heat-labile enterotoxin (Elt or LT) and cholera toxin (Ctx) secreted by ''

Vibrio cholerae ''Vibrio cholerae'' is a species of Gram-negative bacteria, Gram-negative, Facultative anaerobic organism, facultative anaerobe and Vibrio, comma-shaped bacteria. The bacteria naturally live in Brackish water, brackish or saltwater where they att ...

''. 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 The term chloride refers to a compound or molecule that contains either a chlorine anion (), which is a negatively charged chlorine atom, or a non-charged chlorine atom covalently bonded to the rest of the molecule by a single bond (). The pr ...

ions and water from the

enterocyte Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase ...

into the gut lumen. This ionic imbalance causes watery

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

. 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. The importance of these binding events is not yet known.

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 In chemistry, a hydrogen bond (H-bond) is a specific type of molecular interaction that exhibits partial covalent character and cannot be described as a purely electrostatic force. It occurs when a hydrogen (H) atom, covalently bonded to a mo ...

and 6

salt bridge In electrochemistry, a salt bridge or ion bridge is an essential laboratory device discovered over 100 years ago. It contains an electrolyte solution, typically an inert solution, used to connect the Redox, oxidation and reduction Half cell, ...

s with its two neighbours. The A subunit has a less well-defined

secondary structure Protein secondary structure is the local spatial conformation of the polypeptide backbone excluding the side chains. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...

. 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 Catalysis () is the increase in reaction rate, rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst ...

residue in the A1 fragment (Glu112) lies close to a

hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

region, which packs two loops together. It is thought that this region might be important for

catalysis Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

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.

Origin

The cholera toxin is carried by the CTXφ bacteriophage and may be isolated from

plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria and ...

s. The ''E. coli'' LT (elt) is similarly associated with mobile elements, in this case ''Ent'' plasmids that can carry LT, ST, or both. Partial insertion sequences (ISs) flanking the elt genes provide extra transmission capabilities by homologous recombination at their inverted repeats. Οβ phage-induced conversion in ''E. coli'' has been described as well.

Applications

The B subunits of toxins in this family is relatively harmless on its own. CtxB is routinely used as a neuronal tracer. Elt-IB has been looked into as an adjuvant in transdermal vaccines.

References

External links

* UniProtKB: Ctx , Elt-I , Elt-IIa , Elt-IIb {{InterPro content, IPR001835, IPR001144, IPR010503 Protein domains