Heat-stable enterotoxin
Encyclopedia
Heat-stable enterotoxins (STs) are secretory peptides produced by some bacterial strains, such as enterotoxigenic Escherichia coli
which are in general toxic to animals.
These peptides keep their 3D structure and remain active at temperatures as high as 100oC.
, which leads to the intracellular accumulation of cyclic GMP and downstream effects on several signaling pathways. These events lead to the loss of electrolytes and water from intestinal cells.
Heat-stable toxin
1 of entero-aggregative Escherichia coli (EAST1) is a small toxin. It is not, however, solely associated with entero-aggregative E. coli but also with many other diarrhoeic E. coli families. Some studies have established the role of EAST1 in some human outbreaks of diarrhoea. Isolates from farm animal
s have been shown to carry the astA gene
coding for EAST1. However, the relation between the presence of EAST1 and disease
is not conclusive.
, which is the cause of acute diarrhoea in infants and travellers in developing countries
, is a 19-residue peptide
containing three disulphide bridges that are functionally important. STa contains an N-terminal signal peptide
composed of two domains, Pre and Pro, involved in extracellular
toxin
release, and a core enterotoxigenic domain
.
Members of heat-stable enterotoxin B family assume a helical secondary structure, with two alpha helices forming a disulfide cross-linked alpha-helical hairpin. The disulfide bonds are crucial for the toxic activity of the protein, and are required for maintenance of the tertiary structure, and subsequent interaction with the particulate form of guanylate cyclase, increasing cyclic GMP levels within the host intestinal epithelial cells.
Enterotoxigenic Escherichia coli
Enterotoxigenic Escherichia coli is a type of Escherichia coli and the leading bacterial cause of diarrhea in the developing world, as well as the most common cause of traveler's diarrhea. Each year, approximately 210 million cases and 380,000 deaths occur, mostly in children, from ETEC...
which are in general toxic to animals.
These peptides keep their 3D structure and remain active at temperatures as high as 100oC.
Function
Different STs recognize distinct receptors on the surface of animal cells and thereby affect different intracellular signaling pathways. For example, STa enterotoxins bind and activate membrane-bound guanylate cyclaseGuanylate cyclase
-Reaction:Guanylate cyclase catalyzes the reaction of guanosine triphosphate to 3',5'-cyclic guanosine monophosphate and pyrophosphate:-Types:...
, which leads to the intracellular accumulation of cyclic GMP and downstream effects on several signaling pathways. These events lead to the loss of electrolytes and water from intestinal cells.
Heat-stable toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
1 of entero-aggregative Escherichia coli (EAST1) is a small toxin. It is not, however, solely associated with entero-aggregative E. coli but also with many other diarrhoeic E. coli families. Some studies have established the role of EAST1 in some human outbreaks of diarrhoea. Isolates from farm animal
Animal
Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...
s have been shown to carry the astA gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
coding for EAST1. However, the relation between the presence of EAST1 and disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
is not conclusive.
Structure
The mature STa protein from Escherichia coliEscherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
, which is the cause of acute diarrhoea in infants and travellers in developing countries
Developing country
A developing country, also known as a less-developed country, is a nation with a low level of material well-being. Since no single definition of the term developing country is recognized internationally, the levels of development may vary widely within so-called developing countries...
, is a 19-residue peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
containing three disulphide bridges that are functionally important. STa contains an N-terminal signal peptide
Signal peptide
A signal peptide is a short peptide chain that directs the transport of a protein.Signal peptides may also be called targeting signals, signal sequences, transit peptides, or localization signals....
composed of two domains, Pre and Pro, involved in extracellular
Extracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
release, and a core enterotoxigenic domain
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
.
Members of heat-stable enterotoxin B family assume a helical secondary structure, with two alpha helices forming a disulfide cross-linked alpha-helical hairpin. The disulfide bonds are crucial for the toxic activity of the protein, and are required for maintenance of the tertiary structure, and subsequent interaction with the particulate form of guanylate cyclase, increasing cyclic GMP levels within the host intestinal epithelial cells.