Eukaryotic translation elongation factor 2 (eEF2) (eEF2)

Eukaryotic translation elongation factor 2 (eEF2) is a member of the GTP-binding elongation factor family and is essential for protein synthesis in eukaryotic cells. It catalyzes the GTP-dependent translocation of the ribosome along mRNA during the elongation phase of translation (UniProt P13639). A defining characteristic of eEF2 is the presence of diphthamide, a unique post-translationally modified histidine residue (His-715 in humans) that is the sole target for ADP-ribosylation by bacterial toxins like Diphtheria toxin and Pseudomonas exotoxin A (PMID: 28821611). This modification irreversibly inactivates eEF2, leading to the cessation of protein synthesis and induction of apoptosis. This mechanism has been harnessed in the design of therapeutic immunotoxins, such as Tagraxofusp and Moxetumomab pasudotox, which deliver toxin fragments to specific cell types to treat malignancies (FDA, 2018). While eEF2 is ubiquitously expressed, the specificity of these drugs is achieved through the targeting domain, though safety concerns like vascular leak syndrome remain a significant challenge in clinical use.

Other names

eEF-2EF-2Elongation factor 2Diphthamide-modified eEF2EEF2

The diphthamide residue of eEF2 is the specific substrate for ADP-ribosylation catalyzed by the catalytic domains of Diphtheria toxin or Pseudomonas exotoxin A. This covalent modification prevents eEF2 from participating in ribosomal translocation, effectively halting protein synthesis and triggering apoptosis (UniProt P13639; PMID: 28821611).