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 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 Guanylate cyclase (EC 4.6.1.2, also known as guanyl cyclase, guanylyl cyclase, or GC; systematic name GTP diphosphate-lyase (cyclizing; 3′,5′-cyclic-GMP-forming)) is a lyase enzyme that converts guanosine triphosphate (GTP) to cyclic guanos ...

, which leads to the intracellular accumulation of

cyclic GMP Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP. Its most likely mechanism of action is activation of intracellular protein kinases in r ...

and downstream effects on several signaling pathways. These events lead to the loss of electrolytes and water from intestinal cells. Heat-stable

toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849 ...

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 Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...

outbreaks of

diarrhoea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

. Isolates from farm

animal Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...

s have been shown to carry the astA

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

coding for EAST1. However, the relation between the presence of EAST1 and

disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...

is not conclusive.

Structure

The mature STa protein from ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

'', which is the cause of

acute Acute may refer to: Science and technology * Acute angle ** Acute triangle ** Acute, a leaf shape in the glossary of leaf morphology * Acute (medicine), a disease that it is of short duration and of recent onset. ** Acute toxicity, the adverse eff ...

in infants and travellers in

developing countries A developing country is a sovereign state with a lesser developed industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no clear agreem ...

, is a 19-residue

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

containing three

disulphide bridges In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

that are functionally important. STa contains an N-terminal signal peptide composed of two domains, Pre and Pro, involved in extracellular

release, and a core enterotoxigenic protein domain, 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.

References

Protein families Protein domains Bacterial toxins {{protein-stub