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 An enterotoxin is a protein exotoxin released by a microorganism that targets the intestines. They can be chromosomally or plasmid encoded. They are heat labile (> 60 °C), of low molecular weight and water-soluble. Enterotoxins are frequently cy ...

(Elt or LT) and

cholera toxin Cholera toxin (also known as choleragen, CTX, CTx and CT) is a potent enterotoxin produced by the bacterium Vibrio cholerae which causes severe watery diarrhea and dehydration that define cholera infections. The toxin is a member of the heat-l ...

(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 Camp may refer to: Areas of confinement, imprisonment, or for execution * Concentration camp, an internment camp for political prisoners or politically targeted demographics, such as members of national or minority ethnic groups * Extermination ...

levels through

ADP-ribosylation ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. It is a reversible post-translational modification that is involved in many cellular processes, including cell signaling, DNA repair, gene regulation and apoptosis ...

of the alpha-subunit of a

Gs protein GS may stand for: Businesses and organizations * Goldman Sachs, one of the world's largest global investment banks * Global Star Software, a former Canadian video game publisher * GS (Swedish union), a trade union in Sweden * GS Group, a Korea ...

leading to the constitutive activation of

adenylate cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...

. 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 A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

consist of an AB5 multimer structure, in which a

pentamer A pentamer is an entity composed of five subunits. In chemistry, it applies to molecules made of five monomers. In biochemistry, it applies to macromolecules, particularly pentameric proteins, made of five protein sub-units. In microbiology, a ...

of B chains has a membrane-binding function and an A chain is needed for

enzymatic An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as produc ...

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

antigenic In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. Anti ...

ally distinct.

Origin

The cholera toxin is carried by the

CTXφ bacteriophage The CTXφ bacteriophage is a filamentous bacteriophage. It is a positive-strand DNA virus with single-stranded DNA (ssDNA). CTXφ infects some strains of ''Vibrio cholerae'', the bacterium that causes cholera. It carries the genes for chol ...

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