Eukaryotic Translation Elongation Factor 2 (EEF2)

Diphtheria toxin and Pseudomonas exotoxin A (PA toxin) inhibit protein synthesis by catalyzing covalent binding of the ADP-ribose moiety of NAD to elongation factor-2 (EF2). EF2 is required for the translocation step in protein synthesis, where peptidyl-tRNA is moved to the next codon on mRNA from the acceptor site on the ribosome at the expense of the energy provided by hydrolysis of GTP bound to EF2. Class I diphtheria toxin resistance (sensitivity) is related to binding of the toxin, a function coded by chromosome 5. Class II resistance is due to a defect in protein synthesis such that EF2 is not ADP-ribosylated by diphtheria toxin or PA toxin. In one subclass this is due to a mutation in the structural gene for EF2; in a second subclass it is due to mutation in a gene for posttranslational modification of EF2.