Eukaryotic elongation factor 2 (eEF2) (eEF2)

Eukaryotic elongation factor 2 (eEF2) is a member of the GTP-binding translation factor family and is essential for protein synthesis in all eukaryotic cells (UniProt P13639). It catalyzes the GTP-dependent translocation of the ribosome along messenger RNA (mRNA) during the elongation phase of translation (PubMed: 28112733). A defining feature of eEF2 is the presence of a unique post-translational modification called diphthamide, which occurs on a specific histidine residue (His715 in humans) (PubMed: 30531970). This diphthamide residue is the specific target for ADP-ribosylation by certain bacterial virulence factors, including Diphtheria toxin and Pseudomonas Exotoxin A (PubMed: 15596548). Modification of this residue by these toxins or toxin-derived therapeutic agents (such as immunotoxins) irreversibly inactivates eEF2, leading to the cessation of protein synthesis and the induction of apoptosis (PubMed: 25231978). Consequently, eEF2 is a critical target in both infectious disease pathology and the development of targeted cancer therapies like Denileukin diftitox (DrugBank DB00004).

Other names

EEF2Elongation factor 2EF-2Diphthamide-modified eEF2

ADP-ribosylation of the diphthamide residue (His715) by bacterial toxins or toxin-based drugs, which prevents the translocation of peptidyl-tRNA from the A-site to the P-site of the ribosome, thereby halting protein synthesis and inducing apoptosis (PubMed: 15596548, PubMed: 25231978).