Heat-stable enterotoxin

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Heat-stable enterotoxin B, secretory
PDB 1ehs EBI.jpg
Structure of Escherichia coli heat-stable enterotoxin b. [1]
Identifiers
SymbolSTb_secrete
Pfam PF09075
InterPro IPR015160
PROSITE PDOC00246
SCOP2 1ehs / SCOPe / SUPFAM
OPM superfamily 88
OPM protein 1ehs
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Heat-stable enterotoxin ST
PDB 1etm EBI.jpg
structural characteristics for biological activity of heat-stable enterotoxin produced by enterotoxigenic escherichia coli: x-ray crystallography of weakly toxic and nontoxic analogs
Identifiers
SymbolEnterotoxin_ST
Pfam PF02048
InterPro IPR001489
PROSITE PDOC00246
SCOP2 1etn / SCOPe / SUPFAM
OPM superfamily 162
OPM protein 1etn
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Heat stable E.coli enterotoxin 1
Identifiers
SymbolEnterotoxin_HS1
Pfam PF08090
InterPro IPR012557
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Heat-stable enterotoxins (STs) are secretory peptides produced by some bacterial strains, such as enterotoxigenic Escherichia coli [2] which are in general toxic to animals.

Contents

These peptides keep their 3D structure and remain active at temperatures as high as 100 °C.

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 cyclase, which leads to the intracellular accumulation of cyclic GMP and downstream effects on several signaling pathways. [3] [4] [5] [6] 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 animals have been shown to carry the astA gene coding for EAST1. However, the relation between the presence of EAST1 and disease is not conclusive. [7]

Structure

The mature STa protein from Escherichia coli , 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. [8]

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. [9]

Related Research Articles

<span class="mw-page-title-main">Adenylyl cyclase</span> Enzyme with key regulatory roles in most cells

Adenylate cyclase is an enzyme with systematic name ATP diphosphate-lyase . It catalyzes the following reaction:

<span class="mw-page-title-main">Exotoxin</span> Toxin from bacteria that destroys or disrupts cells

An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host–pathogen interface.

<span class="mw-page-title-main">Guanylate cyclase</span> Lyase enzyme that synthesizes cGMP from GTP

Guanylate cyclase is a lyase enzyme that converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) and pyrophosphate:

<span class="mw-page-title-main">Enterotoxin</span> Toxin from a microorganism affecting the intestines

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 (>60⁰), of low molecular weight and water-soluble. Enterotoxins are frequently cytotoxic and kill cells by altering the apical membrane permeability of the mucosal (epithelial) cells of the intestinal wall. They are mostly pore-forming toxins, secreted by bacteria, that assemble to form pores in cell membranes. This causes the cells to die.

Enterotoxigenic Escherichia coli (ETEC) is a type of Escherichia coli and one of the leading bacterial causes of diarrhea in the developing world, as well as the most common cause of travelers' diarrhea. Insufficient data exists, but conservative estimates suggest that each year, about 157,000 deaths occur, mostly in children, from ETEC. A number of pathogenic isolates are termed ETEC, but the main hallmarks of this type of bacterium are expression of one or more enterotoxins and presence of fimbriae used for attachment to host intestinal cells. The bacterium was identified by the Bradley Sack lab in Kolkata in 1968.

<span class="mw-page-title-main">Guanylate cyclase 2C</span>

Guanylate cyclase 2C, also known as guanylyl cyclase C (GC-C), intestinal guanylate cyclase, guanylate cyclase-C receptor, or the heat-stable enterotoxin receptor (hSTAR) is an enzyme that in humans is encoded by the GUCY2C gene.

<span class="mw-page-title-main">Guanylin</span>

Guanylin is a 15 amino acid peptide that is secreted by goblet cells in the colon. Guanylin acts as an agonist of the guanylyl cyclase receptor GC-C and regulates electrolyte and water transport in intestinal and renal epithelia. Upon receptor binding, guanylin increases the intracellular concentration of cGMP, induces chloride secretion and decreases intestinal fluid absorption, ultimately causing diarrhoea. The peptide stimulates the enzyme through the same receptor binding region as the heat-stable enterotoxins.

<span class="mw-page-title-main">GM1</span> Biochemical compound important in the brain and intestines

GM1 (monosialotetrahexosylganglioside) the "prototype" ganglioside, is a member of the ganglio series of gangliosides which contain one sialic acid residue. GM1 has important physiological properties and impacts neuronal plasticity and repair mechanisms, and the release of neurotrophins in the brain. Besides its function in the physiology of the brain, GM1 acts as the site of binding for both cholera toxin and E. coli heat-labile enterotoxin.

The AB5 toxins are six-component protein complexes secreted by certain pathogenic bacteria known to cause human diseases such as cholera, dysentery, and hemolytic–uremic syndrome. One component is known as the A subunit, and the remaining five components are B subunits. All of these toxins share a similar structure and mechanism for entering targeted host cells. The B subunit is responsible for binding to receptors to open up a pathway for the A subunit to enter the cell. The A subunit is then able to use its catalytic machinery to take over the host cell's regular functions.

<span class="mw-page-title-main">GUCY2D</span> Protein-coding gene in the species Homo sapiens

Retinal guanylyl cyclase 1 also known as guanylate cyclase 2D, retinal is an enzyme that in humans is encoded by the GUCY2D gene.

<span class="mw-page-title-main">NPR1</span> Protein-coding gene in the species Homo sapiens

Natriuretic peptide receptor A/guanylate cyclase A , also known as NPR1, is an atrial natriuretic peptide receptor. In humans it is encoded by the NPR1 gene.

<span class="mw-page-title-main">NPR2</span> Protein-coding gene in Homo sapiens

Natriuretic peptide receptor B/guanylate cyclase B , also known as NPR2, is an atrial natriuretic peptide receptor. In humans it is encoded by the NPR2 gene.

<span class="mw-page-title-main">GUCY1B3</span> Protein-coding gene in the species Homo sapiens

Guanylate cyclase soluble subunit beta-1 is an enzyme that in humans is encoded by the GUCY1B3 gene.

<span class="mw-page-title-main">Clostridium enterotoxin</span>

Clostridium enterotoxins are toxins produced by Clostridium species. Clostridial species are one of the major causes of food poisoning/gastrointestinal illnesses. They are anaerobic, gram-positive, spore-forming rods that occur naturally in the soil. Among the family are: Clostridium botulinum, which produces one of the most potent toxins in existence; Clostridium tetani, causative agent of tetanus; and Clostridium perfringens, commonly found in wound infections and diarrhea cases.

<span class="mw-page-title-main">Enterotoxin type B</span>

In the field of molecular biology, enterotoxin type B, also known as Staphylococcal enterotoxin B (SEB), is an enterotoxin produced by the gram-positive bacteria Staphylococcus aureus. It is a common cause of food poisoning, with severe diarrhea, nausea and intestinal cramping often starting within a few hours of ingestion. Being quite stable, the toxin may remain active even after the contaminating bacteria are killed. It can withstand boiling at 100 °C for a few minutes. Gastroenteritis occurs because SEB is a superantigen, causing the immune system to release a large amount of cytokines that lead to significant inflammation.

<span class="mw-page-title-main">Uroguanylin</span> Chemical compound

Uroguanylin is a 16 amino acid peptide that is secreted by enterochromaffin cells in the duodenum and proximal small intestine. Guanylin acts as an agonist of the guanylyl cyclase receptor guanylate cyclase 2C (GC-C), and regulates electrolyte and water transport in intestinal and renal epithelia. By agonizing this guanylyl cyclase receptor, uroguanylin and guanylin cause intestinal secretion of chloride and bicarbonate to dramatically increase; this process is helped by the second messenger cGMP. Its sequence is H-Asn-Asp-Asp-Cys(1)-Glu-Leu-Cys(2)-Val-Asn-Val-Ala-Cys(1)-Thr-Gly-Cys(2)-Leu-OH.

<span class="mw-page-title-main">Heat-labile enterotoxin family</span> Family of toxic protein complexes

In molecular biology, the heat-labile enterotoxin family includes Escherichia coli heat-labile enterotoxin and cholera toxin (Ctx) secreted by Vibrio cholerae.

Enteroaggregative Escherichia coli are a pathotype of Escherichia coli which cause acute and chronic diarrhea in both the developed and developing world. They may also cause urinary tract infections. EAEC are defined by their "stacked-brick" pattern of adhesion to the human laryngeal epithelial cell line HEp-2. The pathogenesis of EAEC involves the aggregation of and adherence of the bacteria to the intestinal mucosa, where they elaborate enterotoxins and cytotoxins that damage host cells and induce inflammation that results in diarrhea.

<span class="mw-page-title-main">GUCY2F</span> Protein-coding gene in humans

Retinal guanylyl cyclase 2 also known as guanylate cyclase F (GUCY2F) is a protein that in humans is encoded by the GUCY2F gene.

Plecanatide, sold under the brand name Trulance, is a medication for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation. It is being launched in India under the brand name "Plecasoft". Plecanatide is an agonist of guanylate cyclase-C. Plecanatide increases intestinal transit and fluid through a buildup of cGMP.

References

  1. Sukumar M, Rizo J, Wall M, Dreyfus LA, Kupersztoch YM, Gierasch LM (September 1995). "The structure of Escherichia coli heat-stable enterotoxin b by nuclear magnetic resonance and circular dichroism". Protein Sci. 4 (9): 1718–29. doi:10.1002/pro.5560040907. PMC   2143221 . PMID   8528070.
  2. Ghanekar Y, Chandrashaker A, Visweswariah SS (September 2003). "Cellular refractoriness to the heat-stable enterotoxin peptide is associated with alterations in levels of the differentially glycosylated forms of guanylyl cyclase C". Eur. J. Biochem. 270 (18): 3848–57. doi: 10.1046/j.1432-1033.2003.03779.x . PMID   12950269.
  3. Hasegawa M, Shimonishi Y (February 2005). "Recognition and signal transduction mechanism of Escherichia coli heat-stable enterotoxin and its receptor, guanylate cyclase C". The Journal of Peptide Research. 65 (2): 261–71. doi:10.1111/j.1399-3011.2005.00218.x. PMID   15705168.
  4. Al-Majali AM, Asem EK, Lamar CH, Robinson JP, Freeman MJ, Saeed AM (June 2000). "Characterization of the interaction of Escherichia coli heat-stable enterotoxin (STa) with its putative receptor on the intestinal tract of newborn calves". FEMS Immunol. Med. Microbiol. 28 (2): 97–104. doi: 10.1111/j.1574-695x.2000.tb01462.x . PMID   10799798.
  5. Al-Majali AM, Ababneh MM, Shorman M, Saeed AM (February 2007). "Interaction of Escherichia coli heat-stable enterotoxin (STa) with its putative receptor on the intestinal tract of newborn kids". FEMS Immunol. Med. Microbiol. 49 (1): 35–40. doi: 10.1111/j.1574-695X.2006.00167.x . PMID   17094787.
  6. Giannella RA, Mann EA (2003). "E. coli heat-stable enterotoxin and guanylyl cyclase C: new functions and unsuspected actions". Trans. Am. Clin. Climatol. Assoc. 114: 67–85, discussion 85-6. PMC   2194511 . PMID   12813912.
  7. Veilleux S, Dubreuil JD (2006). "Presence of Escherichia coli carrying the EAST1 toxin gene in farm animals". Vet. Res. 37 (1): 3–13. doi: 10.1051/vetres:2005045 . PMID   16336921.
  8. Sato T, Shimonishi Y (March 2004). "Structural features of Escherichia coli heat-stable enterotoxin that activates membrane-associated guanylyl cyclase". Journal of Peptide Research. 63 (3): 200–6. doi:10.1111/j.1399-3011.2004.00125.x. PMID   15049831.
  9. Rizo J, Gierasch LM, Sukumar M, Wall M, Dreyfus LA, Kupersztoch YM (1995). "The structure of Escherichia coli heat-stable enterotoxin b by nuclear magnetic resonance and circular dichroism". Protein Sci. 4 (9): 1718–1729. doi:10.1002/pro.5560040907. PMC   2143221 . PMID   8528070.
This article incorporates text from the public domain Pfam and InterPro: IPR001489
This article incorporates text from the public domain Pfam and InterPro: IPR015160
This article incorporates text from the public domain Pfam and InterPro: IPR012557