The AB toxins are two-component
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
complexes secreted by a number of
pathogenic
In biology, a pathogen (, "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.
The term ...
bacteria
Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
, though there is a pore-forming AB toxin found in the eggs of a
snail
A snail is a shelled gastropod. The name is most often applied to land snails, terrestrial molluscs, terrestrial pulmonate gastropod molluscs. However, the common name ''snail'' is also used for most of the members of the molluscan class Gas ...
.
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
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
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 othe ...
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 ...
transport
Transport (in British English) or transportation (in American English) is the intentional Motion, movement of humans, animals, and cargo, goods from one location to another. Mode of transport, Modes of transport include aviation, air, land tr ...
"B" subunit.
T
Examples
* DT-like toxins: all toxins of these class are ADP-ribosyltransferases, which means they damage the cell by attaching an ADP-ribose
moiety onto important target components: in this case eEF2.
** The
Diphtheria toxin
Diphtheria toxin is an exotoxin secreted mainly by '' Corynebacterium diphtheriae'' but also by ''Corynebacterium ulcerans'' and '' Corynebacterium pseudotuberculosis'', the pathogenic bacterium that causes diphtheria. The toxin gene is enco ...
(DT) is an AB toxin. It inhibits protein synthesis in the host cell through ADP-ribosylation of the
eukaryotic elongation factor 2 (eEF2), which is an essential component for protein synthesis. It is slightly unusual in that it combines the A and B parts in the same protein chain: the pre-toxin is cleaved into two parts, then the two parts are joined by a
disulfide bond
In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups.
In inor ...
.
** The
exotoxin A of ''
Pseudomonas aeruginosa
''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...
'' is another example of an AB toxin that targets the eEF2. The "A" part is structurally similar to the DT "A" part; the "B" part is located to the N-terminal direction to the "A" part, unlike DT. The bioinformatically-identified "Cholix" toxin from ''V. cholerae'' is similar.
* AB7 toxins: all toxins of this class share a related heptameric "B" subunit, but differ in the function of their "A" part.
** C2-like toxins: the "A" parts are G-actin ADP-ribosyltransferases, which carry out a modification that prevents actin from polymerizing. Members include ''
C. botulinum''
''
C. perfringens'' iota toxin and ''
Clostridioides difficile
''Clostridioides difficile'' ( syn. ''Clostridium difficile'') is a bacterium known for causing serious diarrheal infections, and may also cause colon cancer. It is known also as ''C. difficile'', or ''C. diff'' (), and is a Gram-positive spec ...
'' ADP-ribosyltransferase.
** Anthrax toxins: The protective antigen (PA) is the "B" component shared by the two "A" toxins in ''B. anthracis'': the edema factor (EF) and the lethal factor (LF).
LF is a Zn metalloprotease that cleaves
MAPKK; EF is an adenylate cyclase that targets protein kinases.
*
AB5 toxins
The AB5 toxins are six-component protein complexes secreted by certain pathogenicity, 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 r ...
– all these toxins share a related pentameric "B" subunit, but differ in the function of their "A" part.
*
Ricin
Ricin ( ) is a lectin (a carbohydrate-binding protein) and a highly potent toxin produced in the seeds of the castor oil plant, ''Ricinus communis''. The median lethal dose (LD50) of ricin for mice is around 22 micrograms per kilogram of body ...
is expressed a single polypeptide that gets cleaved into two parts, one acting as "A" and the other acting as "B".
Abrin
Abrin is an extremely toxic toxalbumin found in the seeds of the rosary pea (or jequirity pea), '' Abrus precatorius''. It has a median lethal dose of 0.7 micrograms per kilogram of body mass when given to mice intravenously (approximate ...
is similar.
*
''Clostridium'' neurotoxins, i.e. the
tetanus toxin
Tetanus toxin (TeNT) is an extremely potent neurotoxin produced by the vegetative cell of '' Clostridium tetani'' in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normal ...
and the
botulinum toxin
Botulinum toxin, or botulinum neurotoxin (commonly called botox), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon en ...
, are expressed a single polypeptide that gets cleaved into two parts, one acting as "A" and the other acting as "B".
Research
The two-phase
mechanism of action
In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical Drug interaction, interaction through which a Medication, drug substance produces its pharmacological effect. A mechanism of action usually includes mention o ...
of AB toxins is of particular interest in
cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
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; the term is most familiar as a characterization of cancer.
A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...
cells. This approach combines results from
cancer immunotherapy
Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the basic research, fundamental research of cancer im ...
with the high toxicity of AB toxins, giving raise to a new class of
chimeric protein 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 ...
.
See also
*
Toxalbumin
*
Perivitellin-2
References
{{DEFAULTSORT:Ab Toxin
Bacterial toxins
Protein families