Eukaryotic translation elongation factor 2 (eEF2)

Eukaryotic translation elongation factor 2 (eEF2) is a highly conserved GTPase that mediates the translocation step of translation elongation on ribosomes in eukaryotic cells[3][5][6][8]. It catalyzes the GTP-dependent movement of the ribosome along mRNA, shifting the peptidyl-tRNA from the A-site to the P-site, thereby enabling protein synthesis to proceed[7][2]. eEF2 activity is tightly regulated by phosphorylation—primarily via eEF2 kinase (eEF2K)—in response to cellular stress and nutrient signals, leading to reversible inhibition of translation elongation[1][4]. A unique post-translational modification, diphthamide, is present on a conserved histidine residue in eEF2, providing the specific target for inactivation by diphtheria toxin and Pseudomonas aeruginosa exotoxin A, making infectious toxins deadly by completely shutting down protein synthesis in host cells[5][3]. Disruption of eEF2 function or regulation is implicated in several pathologies, including cancer, where altered translation controls growth, and neurodegenerative diseases, where dysregulated elongation may contribute to pathology[4][1]. Given its essential cellular role and involvement in disease processes, eEF2 is a validated therapeutic target in oncology, infectious disease, and emerging areas in neurology[1][4].

Other names

Elongation factor 2EF-2Peptide elongation factor 2

GTP-dependent translocase activity inhibition, ADP-ribosylation of diphthamide residue (by toxins), Phosphorylation-mediated inactivation (by eEF2 kinase)