Heat-stable enterotoxin
{{Short description|Class of bacterial toxins}}
{{Pfam_box
| Symbol = STb_secrete
| Name = Heat-stable enterotoxin B, secretory
| image = PDB_1ehs_EBI.jpg
| width =
| caption = Structure of Escherichia coli heat-stable enterotoxin b.{{cite journal |vauthors=Sukumar M, Rizo J, Wall M, Dreyfus LA, Kupersztoch YM, Gierasch LM |title=The structure of Escherichia coli heat-stable enterotoxin b by nuclear magnetic resonance and circular dichroism |journal=Protein Sci. |volume=4 |issue=9 |pages=1718–29 |date=September 1995 |pmid=8528070 |pmc=2143221 |doi=10.1002/pro.5560040907 }}
| Pfam= PF09075
| InterPro= IPR015160
| SMART=
| PROSITE=PDOC00246
| SCOP = 1ehs
| TCDB =
| OPM family= 88
| OPM protein= 1ehs
| PDB=
}}
{{Infobox protein family
| Symbol = Enterotoxin_ST
| Name = Heat-stable enterotoxin ST
| image = PDB 1etm EBI.jpg
| width =
| caption = structural characteristics for biological activity of heat-stable enterotoxin produced by enterotoxigenic escherichia coli: x-ray crystallography of weakly toxic and nontoxic analogs
| Pfam = PF02048
| Pfam_clan =
| InterPro = IPR001489
| SMART =
| PROSITE = PDOC00246
| MEROPS =
| SCOP = 1etn
| TCDB =
| OPM family = 162
| OPM protein = 1etn
| CAZy =
| CDD =
}}
{{Infobox protein family
| Symbol = Enterotoxin_HS1
| Name = Heat stable E.coli enterotoxin 1
| image =
| width =
| caption =
| Pfam = PF08090
| Pfam_clan =
| InterPro = IPR012557
| SMART =
| PROSITE =
| MEROPS =
| SCOP =
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
}}
Heat-stable enterotoxins (STs) are secretory peptides produced by some bacterial strains, such as enterotoxigenic Escherichia coli{{cite journal |vauthors=Ghanekar Y, Chandrashaker A, Visweswariah SS |title=Cellular refractoriness to the heat-stable enterotoxin peptide is associated with alterations in levels of the differentially glycosylated forms of guanylyl cyclase C |journal=Eur. J. Biochem. |volume=270 |issue=18 |pages=3848–57 |date=September 2003 |pmid=12950269 |doi=10.1046/j.1432-1033.2003.03779.x |doi-access=free }} which are in general toxic to animals.
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.{{cite journal |vauthors=Hasegawa M, Shimonishi Y |title=Recognition and signal transduction mechanism of Escherichia coli heat-stable enterotoxin and its receptor, guanylate cyclase C |journal=The Journal of Peptide Research |volume=65 |issue=2 |pages=261–71 |date=February 2005 |pmid=15705168 |doi=10.1111/j.1399-3011.2005.00218.x }}{{cite journal |vauthors=Al-Majali AM, Asem EK, Lamar CH, Robinson JP, Freeman MJ, Saeed AM | title = Characterization of the interaction of Escherichia coli heat-stable enterotoxin (STa) with its putative receptor on the intestinal tract of newborn calves | journal = FEMS Immunol. Med. Microbiol. | volume = 28 | issue = 2 | pages = 97–104 |date=June 2000 | pmid = 10799798 | doi = 10.1111/j.1574-695x.2000.tb01462.x| doi-access = free }}{{cite journal |vauthors=Al-Majali AM, Ababneh MM, Shorman M, Saeed AM | title = Interaction of Escherichia coli heat-stable enterotoxin (STa) with its putative receptor on the intestinal tract of newborn kids | journal = FEMS Immunol. Med. Microbiol. | volume = 49 | issue = 1 | pages = 35–40 |date=February 2007 | pmid = 17094787 | doi = 10.1111/j.1574-695X.2006.00167.x | doi-access = free }}{{cite journal |vauthors=Giannella RA, Mann EA | title = E. coli heat-stable enterotoxin and guanylyl cyclase C: new functions and unsuspected actions | journal = Trans. Am. Clin. Climatol. Assoc. | volume = 114 | pages = 67-85; discussion 85-6 | year = 2003 | pmid = 12813912 | pmc = 2194511 }} 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.{{cite journal |vauthors=Veilleux S, Dubreuil JD | title = Presence of Escherichia coli carrying the EAST1 toxin gene in farm animals | journal = Vet. Res. | volume = 37 | issue = 1 | pages = 3–13 | year = 2006 | pmid = 16336921 | doi = 10.1051/vetres:2005045 | doi-access = free }}
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.{{cite journal |vauthors=Sato T, Shimonishi Y | title = Structural features of Escherichia coli heat-stable enterotoxin that activates membrane-associated guanylyl cyclase | journal = Journal of Peptide Research | volume = 63 | issue = 3 | pages = 200–6 |date=March 2004 | pmid = 15049831 | doi = 10.1111/j.1399-3011.2004.00125.x }}
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.{{cite journal |vauthors=Rizo J, Gierasch LM, Sukumar M, Wall M, Dreyfus LA, Kupersztoch YM |title=The structure of Escherichia coli heat-stable enterotoxin b by nuclear magnetic resonance and circular dichroism |journal=Protein Sci. |volume=4 |issue=9 |pages= 1718–1729|year=1995 |pmid=8528070 |pmc=2143221 |doi=10.1002/pro.5560040907}}
References
{{reflist}}
{{Toxins}}
{{InterPro content|IPR001489}}
{{InterPro content|IPR015160}}
{{InterPro content|IPR012557}}