AB toxin
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The AB toxins are two-component protein complexes secreted by a number of pathogenic bacteria, though there is a pore-forming AB toxin found in the eggs of a snail.[1] They can be classified as Type III toxins because they interfere with internal cell function.[2] 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.[2][3] The "A" subunit possesses enzyme activity, and is transferred to the host cell following a conformational change in the membrane-bound transport "B" subunit.[4] T
| C2-like exotoxin "A" part | |||||||||
|---|---|---|---|---|---|---|---|---|---|
crystal structure of the enzymatic component of iota-toxin from clostridium perfringens with nadh | |||||||||
| Identifiers | |||||||||
| Symbol | ADPrib_exo_Tox | ||||||||
| Pfam | PF03496 | ||||||||
| Pfam clan | CL0084 | ||||||||
| InterPro | IPR003540 | ||||||||
| SCOP2 | 1giq / SCOPe / SUPFAM | ||||||||
| |||||||||
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.[5]
- The Diphtheria toxin (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.[5]
- The exotoxin A of Pseudomonas aeruginosa 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.[5]
- AB7 toxins: all toxins of this class share a related heptameric "B" subunit, but differ in the function of their "A" part.[4]
- 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[6] C. perfringens iota toxin and Clostridioides difficile ADP-ribosyltransferase.[7][5]
- 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).[8][9] LF is a Zn metalloprotease that cleaves MAPKK; EF is an adenylate cyclase that targets protein kinases.
- AB5 toxins ā all these toxins share a related pentameric "B" subunit, but differ in the function of their "A" part.
- Ricin is expressed a single polypeptide that gets cleaved into two parts, one acting as "A" and the other acting as "B". Abrin is similar.
- Clostridium neurotoxins, i.e. the tetanus toxin and the botulinum toxin, 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 of AB toxins is of particular interest in cancer 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 with the high toxicity of AB toxins, giving raise to a new class of chimeric protein drugs, called immunotoxins.[10]
See also
References
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