Pseudomonas exotoxin A protein (ETA)

Pseudomonas exotoxin A protein (ETA) is a single-chain, 613-amino-acid protein secreted by Pseudomonas aeruginosa, a Gram-negative bacterium. It belongs to the two-component AB toxin family, comprising an enzymatic domain (A) and a cell-binding/translocation domain (B). The toxin is divided into three domains: domain I mediates receptor binding to the host cell (notably CD91/α2-macroglobulin receptor), domain II mediates membrane translocation, and domain III is responsible for ADP-ribosyltransferase activity. Once internalized, exotoxin A exploits host trafficking pathways to reach the cytosol, where it irreversibly ADP-ribosylates diphthamide on eukaryotic elongation factor 2 (eEF2), resulting in the cessation of protein synthesis and subsequent cell death. As the major virulence factor of P. aeruginosa, exotoxin A plays a critical role in acute and chronic infections, contributing to tissue damage, immune evasion, and disease severity. Its potent cytotoxicity has also led to its use as a payload in experimental immunotoxins for cancer therapy, though immunogenicity and off-target effects have been therapeutic challenges.

Other names

Exotoxin AETAPEPseudomonas exotoxinNAD(+)--diphthamide ADP-ribosyltransferase

Irreversible ADP-ribosylation of eukaryotic elongation factor 2 (eEF2), inhibiting translation and protein synthesis, leading to cell death