AB toxin explained

Symbol:	ADPrib_exo_Tox
C2-like exotoxin "A" part
Pfam:	PF03496
Pfam Clan:	CL0084
Interpro:	IPR003540
Scop:	1giq

Symbol:	Binary_toxB
AB7-type toxin, "B" part
Pfam:	PF03495
Interpro:	IPR003896
Scop:	1acc
Tcdb:	1.C.42

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

Examples

• DT-like toxins: all toxins of these class are ADP-ribosyltransferases, which means they damage the cell by attaching a 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 structually 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.
  • 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 a 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.^[10]

See also

• Toxalbumin
• Perivitellin-2

Notes and References

1. Giglio . M.L. . Ituarte . S. . Milesi . V. . Dreon . M.S. . Brola . T.R. . Caramelo . J. . Ip . J.C.H. . Maté . S. . Qiu . J.W. . Otero . L.H. . Heras . H. . August 2020 . Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails . Journal of Structural Biology . en . 211 . 2 . 107531 . 10.1016/j.jsb.2020.107531. 32446810 . 11336/143650 . free .
2. Web site: Bacterial Pathogenesis: Bacterial Factors that Damage the Host - Producing Exotoxins - A-B Toxins . 2008-12-13 . dead . https://web.archive.org/web/20100727001308/http://student.ccbcmd.edu/courses/bio141/lecguide/unit2/bacpath/abtox.html . 2010-07-27 .
3. De Haan L, Hirst TR . Cholera toxin: a paradigm for multi-functional engagement of cellular mechanisms (Review) . Mol. Membr. Biol. . 21 . 2 . 77–92 . 2004 . 15204437 . 10.1080/09687680410001663267 . 22270979 . free .
4. Perelle S, Gibert M, Boquet P, Popoff MR . Characterization of Clostridium perfringens iota-toxin genes and expression in Escherichia coli . Infect. Immun. . 61 . 12 . 5147–56 . December 1993 . 8225592 . 281295 . 10.1128/IAI.61.12.5147-5156.1993.
5. Simon . NC . Aktories . K . Barbieri . JT . Novel bacterial ADP-ribosylating toxins: structure and function. . Nature Reviews. Microbiology . September 2014 . 12 . 9 . 599–611 . 10.1038/nrmicro3310 . 25023120. 5846498 .
6. Fujii N, Kubota T, Shirakawa S, Kimura K, Ohishi I, Moriishi K, Isogai E, Isogai H . 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 . March 1996 . 8645309 . 10.1006/bbrc.1996.0409 .
7. Stubbs S, Rupnik M, Gibert M, Brazier J, Duerden B, Popoff M . Production of actin-specific ADP-ribosyltransferase (binary toxin) by strains of Clostridium difficile . FEMS Microbiol. Lett. . 186 . 2 . 307–12 . May 2000 . 10802189 . 10.1111/j.1574-6968.2000.tb09122.x. free .
8. Pezard C, Berche P, Mock M . Contribution of individual toxin components to virulence of Bacillus anthracis . Infect. Immun. . 59 . 10 . 3472–7 . October 1991 . 1910002 . 258908 . 10.1128/IAI.59.10.3472-3477.1991.
9. Welkos SL, Lowe JR, Eden-McCutchan F, Vodkin M, Leppla SH, Schmidt JJ . Sequence and analysis of the DNA encoding protective antigen of Bacillus anthracis . Gene . 69 . 2 . 287–300 . September 1988 . 3148491 . 10.1016/0378-1119(88)90439-8 . https://web.archive.org/web/20170923033835/http://www.dtic.mil/get-tr-doc/pdf?AD=ADA204674. dead. September 23, 2017.
10. Zahaf N, Schmidt G . 2017-07-18 . Bacterial Toxins for Cancer Therapy . Toxins (Basel) . 9 . 8 . 236 . 10.3390/toxins9080236 . 5577570 . 28788054 . free .