AB toxin

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 (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.
  • 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.
• 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 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 – 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.

References

References

1. (August 2020). "Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails". Journal of Structural Biology.
2. "Bacterial Pathogenesis: Bacterial Factors that Damage the Host - Producing Exotoxins - A-B Toxins".
3. (2004). "Cholera toxin: a paradigm for multi-functional engagement of cellular mechanisms (Review)". Mol. Membr. Biol..
4. (December 1993). "Characterization of Clostridium perfringens iota-toxin genes and expression in Escherichia coli". Infect. Immun..
5. (September 2014). "Novel bacterial ADP-ribosylating toxins: structure and function.". Nature Reviews. Microbiology.
6. (March 1996). "Characterization of component-I gene of botulinum C2 toxin and PCR detection of its gene in clostridial species". Biochem. Biophys. Res. Commun..
7. (May 2000). "Production of actin-specific ADP-ribosyltransferase (binary toxin) by strains of Clostridium difficile". FEMS Microbiol. Lett..
8. (October 1991). "Contribution of individual toxin components to virulence of Bacillus anthracis". Infect. Immun..
9. (September 1988). "Sequence and analysis of the DNA encoding protective antigen of Bacillus anthracis". Gene.
10. (2017-07-18). "Bacterial Toxins for Cancer Therapy". Toxins (Basel).