AB toxin

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

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

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

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.^[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 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.^[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 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.^[10]

See also

• Toxalbumin
• Perivitellin-2