TheAB toxins are two-componentprotein complexes secreted by a number ofpathogenicbacteria, though there is a pore-forming AB toxin found in the eggs of asnail.[1] They can be classified asType 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 possessesenzyme activity, and is transferred to the hostcell following aconformational change in themembrane-boundtransport "B" subunit.[4]
DT-like toxins: all toxins of these class are ADP-ribosyltransferases, which means they damage the cell by attaching an ADP-ribosemoiety onto important target components: in this case eEF2.[5]
TheDiphtheria toxin (DT) is an AB toxin. It inhibits protein synthesis in the host cell throughADP-ribosylation of theeukaryotic 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 adisulfide bond.[5]
Theexotoxin A ofPseudomonas 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 fromV. 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 includeC. botulinum[6]C. perfringens iota toxin andClostridioides difficile ADP-ribosyltransferase.[7][5]
Anthrax toxins: The protective antigen (PA) is the "B" component shared by the two "A" toxins inB. anthracis: the edema factor (EF) and the lethal factor (LF).[8][9] LF is a Zn metalloprotease that cleavesMAPKK; EF is an adenylate cyclase that targets protein kinases.
AB5 toxins – 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.
The two-phasemechanism of action of AB toxins is of particular interest incancer therapy research. The general idea is to modify the B component of existing toxins to selectively bind tomalignant cells. This approach combines results fromcancer immunotherapy with the high toxicity of AB toxins, giving raise to a new class ofchimeric protein drugs, calledimmunotoxins.[10]
^Fujii N, Kubota T, Shirakawa S, Kimura K, Ohishi I, Moriishi K, Isogai E, Isogai H (March 1996). "Characterization of component-I gene of botulinum C2 toxin and PCR detection of its gene in clostridial species".Biochem. Biophys. Res. Commun.220 (2):353–9.doi:10.1006/bbrc.1996.0409.PMID8645309.
