The AB toxins are two-component

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

complexes secreted by a number of

pathogenic In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ger ...

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...

, though there is a pore-forming AB toxin found the eggs of a

snail A snail is, in loose terms, a shelled gastropod. The name is most often applied to land snails, terrestrial pulmonate gastropod molluscs. However, the common name ''snail'' is also used for most of the members of the molluscan class ...

. They can be classified as Type III toxins because they interfere with internal cell function. They are named AB toxins due to their components: the "A" component is usually the "active" portion, and the "B" component is usually the "binding" portion. The "A" subunit possesses

enzyme Enzymes () are proteins that act as biological catalysts 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 products ...

activity, and is transferred to the host

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

following a

conformational change In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors. A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or oth ...

in the membrane-bound

transport Transport (in British English), or transportation (in American English), is the intentional movement of humans, animals, and goods from one location to another. Modes of transport include air, land ( rail and road), water, cable, pipelin ...

"B" subunit. These

s consist of two independent polypeptides, which correspond to the A/B subunit moieties. The enzyme component (A) enters the

through

endosome Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...

s produced by the oligomeric binding/translocation protein (B), and prevents

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...

polymerisation through ADP-ribosylation of monomeric G-actin. Examples of the "A" component of an AB toxin include '' C. perfringens'' iota toxin Ia, '' C. botulinum'' C2 toxin CI, and '' Clostridium difficile'' ADP-ribosyltransferase. Other homologous

s have been found in ''Clostridium spiroforme''. An example of the B component of an AB toxin is ''

Bacillus anthracis ''Bacillus anthracis'' is a gram-positive and rod-shaped bacterium that causes anthrax, a deadly disease to livestock and, occasionally, to humans. It is the only permanent ( obligate) pathogen within the genus '' Bacillus''. Its infection is a ...

'' protective

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...

(PA) protein, ''B. anthracis'' secretes three toxin factors: the protective antigen (PA); the oedema factor (EF); and the lethal factor (LF). Each is a thermolabile protein of ~80kDa. PA forms the "B" part of the exotoxin and allows passage of the "A" moiety (consisting of EF or LF) into target

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

. PA protein forms the central part of the complete anthrax toxin, and translocates the A moiety into host

s after assembling as a heptamer in the

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. ...

. The

Diphtheria toxin Diphtheria toxin is an exotoxin secreted by ''Corynebacterium diphtheriae'', the pathogenic bacterium that causes diphtheria. The toxin gene is encoded by a prophageA prophage is a virus that has inserted itself into the genome of the h ...

also is an AB toxin. It inhibits protein synthesis in the host cell through phosphorylation of the

eukaryotic elongation factor 2 Eukaryotic elongation factor 2 is a protein that in humans is encoded by the ''EEF2'' gene. It is the archaeal and eukaryotic counterpart of bacterial EF-G. This gene encodes a member of the GTP-binding translation elongation factor family. Thi ...

, which is an essential component for protein synthesis. The

exotoxin A The Pseudomonas exotoxin (or exotoxin A) is an exotoxin produced by ''Pseudomonas aeruginosa''. ''Vibrio cholerae'' produces a similar protein called the Cholix toxin (). It inhibits elongation factor-2. It does so by ADP-ribosylation of EF2 u ...

of ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic– facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. a ...

'' is another example of an AB toxin that targets the eukaryotic elongation factor 2. The

AB5 toxin 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 fi ...

s are usually considered a type of AB toxin, characterized by B pentamers. Less commonly, the term "AB toxin" is used to emphasize the monomeric character of the B component. The two-phase

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targ ...

of AB toxins is of particular interest in

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

therapy research. The general idea is to modify the B component of existing toxins to selectively bind to

malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

cells. This approach combines results from

cancer immunotherapy Cancer immunotherapy (sometimes called immuno-oncology) is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer ...

with the high toxicity of AB toxins, giving raise to a new class of

chimeric protein Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this '' fusion gene'' ...

drugs, called

immunotoxins An immunotoxin is an artificial protein consisting of a targeting portion linked to a toxin. When the protein binds to that cell, it is taken in through endocytosis, and the toxin kills the cell. They are used for the treatment of some kinds of c ...

References

{{DEFAULTSORT:Ab Toxin Bacterial toxins Protein families

See also

References