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, respo ...
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 germ ...
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 among ...
, 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 Gastro ...
.
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. A ...
activity, and is transferred to the host
cell 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
A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates the interior of a cell from the external environment or creates intracellular compartments by serving as a boundary between one part of the c ...
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, pipeline, an ...
"B" subunit.
These
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, respo ...
s consist of two independent polypeptides, which correspond to the A/B subunit
moieties. The enzyme component (A) enters the
cell through
endosomes 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 over ...
polymerisation through ADP-ribosylation of monomeric G-actin.
Examples of the "A" component of an AB toxin include ''
C. perfringens
''Clostridium perfringens'' (formerly known as ''C. welchii'', or ''Bacillus welchii'') is a Gram-positive, rod-shaped, anaerobic, spore-forming pathogenic bacterium of the genus ''Clostridium''. ''C. perfringens'' is ever-present in nature and ...
'' iota toxin Ia,
''
C. botulinum
''Clostridium botulinum'' is a Gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce the neurotoxin botulinum.
The botulinum toxin can cause botulism, a severe flaccid paralytic disease in humans an ...
'' C2 toxin CI,
and ''
Clostridium difficile
''Clostridioides difficile'' (syn. ''Clostridium difficile'') is a bacterium that is well known for causing serious diarrheal infections, and may also cause colon cancer. Also known as ''C. difficile'', or ''C. diff'' (), is Gram-positive spec ...
'' ADP-ribosyltransferase.
Other
homologous 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, respo ...
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 response. ...
(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
cells after assembling as a heptamer in the
membrane.
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 host ...
also is an AB toxin. It inhibits protein synthesis in the host cell through phosphorylation of the
eukaryotic elongation factor 2, which is an essential component for protein synthesis. The
exotoxin A 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. aerugi ...
'' is another example of an AB toxin that targets the eukaryotic elongation factor 2.
The
AB5 toxins 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 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 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 im ...
with the high toxicity of AB toxins, giving raise to a new class of
chimeric protein drugs, called
immunotoxins.
See also
*
Toxalbumin
Toxalbumins are toxic plant proteins that disable ribosomes and thereby inhibit protein synthesis, producing severe cytotoxic effects in multiple organ systems. They are dimers held together by a disulfide bond and comprise a lectin (carbohyd ...
*
Perivitellin-2
Perivitellin-2 (PV2) is a pore-forming toxin present in the egg perivitelline fluid of the apple snails '' Pomacea maculata'' (PmPV2) and ''Pomacea canaliculata'' (PcPV2). This protein, called perivitellin, is massively acumulated in the eggs (~2 ...
References
{{DEFAULTSORT:Ab Toxin
Bacterial toxins
Protein families