AB toxin
(Redirected from AB-type toxins)
| 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 | ||||||||
| |||||||||
| AB7-type toxin, "B" part | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 crystal structure of the anthrax toxin protective antigen heptameric prepore | |||||||||
| Identifiers | |||||||||
| Symbol | Binary_toxB | ||||||||
| Pfam | PF03495 | ||||||||
| InterPro | IPR003896 | ||||||||
| SCOP2 | 1acc / SCOPe / SUPFAM | ||||||||
| 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
[edit]- 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.[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 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
[edit]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
[edit]References
[edit]- ^ 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. 211 (2): 107531. doi:10.1016/j.jsb.2020.107531. hdl:11336/143650. PMID 32446810.
- ^ a b "Bacterial Pathogenesis: Bacterial Factors that Damage the Host - Producing Exotoxins - A-B Toxins". Archived from the original on 2010-07-27. Retrieved 2008-12-13.
- ^ De Haan L, Hirst TR (2004). "Cholera toxin: a paradigm for multi-functional engagement of cellular mechanisms (Review)". Mol. Membr. Biol. 21 (2): 77–92. doi:10.1080/09687680410001663267. PMID 15204437. S2CID 22270979.
- ^ a b Perelle S, Gibert M, Boquet P, Popoff MR (December 1993). "Characterization of Clostridium perfringens iota-toxin genes and expression in Escherichia coli". Infect. Immun. 61 (12): 5147–56. doi:10.1128/IAI.61.12.5147-5156.1993. PMC 281295. PMID 8225592.
- ^ a b c d Simon, NC; Aktories, K; Barbieri, JT (September 2014). "Novel bacterial ADP-ribosylating toxins: structure and function". Nature Reviews. Microbiology. 12 (9): 599–611. doi:10.1038/nrmicro3310. PMC 5846498. PMID 25023120.
- ^ 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. PMID 8645309.
- ^ Stubbs S, Rupnik M, Gibert M, Brazier J, Duerden B, Popoff M (May 2000). "Production of actin-specific ADP-ribosyltransferase (binary toxin) by strains of Clostridium difficile". FEMS Microbiol. Lett. 186 (2): 307–12. doi:10.1111/j.1574-6968.2000.tb09122.x. PMID 10802189.
- ^ Pezard C, Berche P, Mock M (October 1991). "Contribution of individual toxin components to virulence of Bacillus anthracis". Infect. Immun. 59 (10): 3472–7. doi:10.1128/IAI.59.10.3472-3477.1991. PMC 258908. PMID 1910002.
- ^ Welkos SL, Lowe JR, Eden-McCutchan F, Vodkin M, Leppla SH, Schmidt JJ (September 1988). "Sequence and analysis of the DNA encoding protective antigen of Bacillus anthracis". Gene. 69 (2): 287–300. doi:10.1016/0378-1119(88)90439-8. PMID 3148491. Archived from the original on September 23, 2017.
- ^ Zahaf N, Schmidt G (2017-07-18). "Bacterial Toxins for Cancer Therapy". Toxins (Basel). 9 (8): 236. doi:10.3390/toxins9080236. PMC 5577570. PMID 28788054.
