Which toxin is commonly used in immunotoxins?
Selecting optimal toxin component for immunoconjugate involves potency, intracellular stability, lack of mammalian cell surface receptors to avoid nonspecific uptake, and ability to produce recombinant fusion maintaining disulfide integrity. Diphtheria toxin secreted by toxigenic Corynebacterium diphtheriae, 58 kDa single polypeptide proteolytically cleaved into 21 kDa catalytic A fragment and 37 kDa binding-translocation B fragment linked by single disulfide Cys186-Cys201. Catalytic activity transfers ADP-ribose to elongation factor 2 with turnover number approximately 1000 per minute. Native receptor heparin binding EGF-like precursor widely expressed, so receptor-binding domain residues 1-389 deleted to generate DT388 retaining translocation domain helices capable of endosomal membrane insertion at acidic pH after furin cleavage. Similarly Pseudomonas exotoxin A 66 kDa secreted by Pseudomonas aeruginosa, ADP-ribosylates EF2 after binding CD91 receptor, truncated to PE38 removing domain Ia binding region retaining domain II translocation and domain III catalytic with C-terminal REDLK endoplasmic reticulum retrieval motif. Plant toxins like ricin A chain or gelonin inactivate ribosomes via depurination but require chemical conjugation via heterobifunctional crosslinkers SPDP forming disulfide bridge.
Ref: Weldon & Pastan FEBS J 2011 PE38 DT388 catalytic domain; Collier EF2 ADP-ribosylation translation arrest mechanism.