ABSTRACT
Pseudomonas exotoxin A (ETA) has interesting similarities to and differences with diphtheria toxin in its mechanism of killing cells. The N-terminal domain of ETA appears to include the cell surface-binding domain, although direct demonstration of this activity in a specific domain is lacking because of the difficulty in measuring ETA binding to cells. Domain II has been proposed to play a role in the entry of domain III into the cytosol based upon the loss of toxicity of domain II mutants without loss in cell surface-binding activity or loss of adenosine diphosphate (ADP)-ribosylation activity. Expression of C-terminal fragments of the toxin that correspond with domain III of the crystal structure demonstrates that the last 306 amino acids contain the ADP-ribosylation activity. The long history of research in DT mechanism relative to the recent burst of interest in ETA is reflected in the approaches taken to probe structure-function relationships.
