AB toxin (original) (raw)

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Protein family

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
Available protein structures:Pfam structures / ECOD PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Protein family

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
Available protein structures:Pfam structures / ECOD PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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

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".

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]

^ 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.