InterPro domain: IPR005517

Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome [ 1 , 2 , 3 ]. EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.

Elongation factor EF2 (EF-G) is a G-protein. It brings about the translocation of peptidyl-tRNA and mRNA through a ratchet-like mechanism: the binding of GTP-EF2 to the ribosome causes a counter-clockwise rotation in the small ribosomal subunit; the hydrolysis of GTP to GDP by EF2 and the subsequent release of EF2 causes a clockwise rotation of the small subunit back to the starting position [ 4 , 5 ]. This twisting action destabilises tRNA-ribosome interactions, freeing the tRNA to translocate along the ribosome upon GTP-hydrolysis by EF2. EF2 binding also affects the entry and exit channel openings for the mRNA, widening it when bound to enable the mRNA to translocate along the ribosome.

EF2 has five domains. This entry represents domain IV found in EF2 (or EF-G) of both prokaryotes and eukaryotes. The EF2-GTP-ribosome complex undergoes extensive structural rearrangement for tRNA-mRNA movement to occur. Domain IV, which extends from the 'body' of the EF2 molecule much like a lever arm, facilitates the movement of peptidyl-tRNA from the A to the P site, being critical for the structural transition to take place [ 6 ].

Included in this entry is a domain of mitochondrial Elongation factor G1 (mtEFG1) proteins that is homologous to domain IV of EF-G. Eukaryotic cells harbor 2 protein synthesis systems: one localized in the cytoplasm, the other in the mitochondria. Most factors regulating mitochondrial protein synthesis are encoded by nuclear genes, translated in the cytoplasm, and then transported to the mitochondria. The eukaryotic system of elongation factor (EF) components is more complex than that in prokaryotes, with both cytoplasmic and mitochondrial elongation factors and multiple isoforms being expressed in certain species. During the process of peptide synthesis and tRNA site changes, the ribosome is moved along the mRNA a distance equal to one codon with the addition of each amino acid. In bacteria this translocation step is catalyzed by EF-G_GTP, which is hydrolyzed to provide the required energy. Thus, this action releases the uncharged tRNA from the P site and transfers the newly formed peptidyl-tRNA from the A site to the P site. Eukaryotic mtEFG1 proteins show significant homology to bacterial EF-Gs. Mutants in yeast mtEFG1 have impaired mitochondrial protein synthesis, respiratory defects and a tendency to lose mitochondrial DNA [ 7 , 8 , 9 , 9 , 10 , 11 , 12 , 13 , 14 ].

1. Structural studies of eukaryotic elongation factors. Cold Spring Harb. Symp. Quant. Biol. 66, 425-37
2. Elongation factors on the ribosome. Curr. Opin. Struct. Biol. 15, 349-54
3. Elongation factors in protein biosynthesis. Trends Biochem. Sci. 28, 434-41
4. Ratchet-like movements between the two ribosomal subunits: their implications in elongation factor recognition and tRNA translocation. Cold Spring Harb. Symp. Quant. Biol. 66, 67-75
5. Mechanism of elongation factor G function in tRNA translocation on the ribosome. Cold Spring Harb. Symp. Quant. Biol. 66, 449-58
6. Following movement of domain IV of elongation factor G during ribosomal translocation. Proc. Natl. Acad. Sci. U.S.A. 111, 15060-5
7. Identification and characterization of two novel human mitochondrial elongation factor genes, hEFG2 and hEFG1, phylogenetically conserved through evolution. Hum. Genet. 109, 542-50
8. Mitochondrial translational-initiation and elongation factors in Saccharomyces cerevisiae. Eur. J. Biochem. 201, 643-52
9. Early evolutionary relationships among known life forms inferred from elongation factor EF-2/EF-G sequences: phylogenetic coherence and structure of the archaeal domain. J. Mol. Evol. 34, 396-405
10. Evolution of translational elongation factor (EF) sequences: reliability of global phylogenies inferred from EF-1 alpha(Tu) and EF-2(G) proteins. Proc. Natl. Acad. Sci. U.S.A. 91, 3255-9
11. Ribosomal translocation: EF-G turns the crank. Curr. Biol. 10, R369-73
12. Translational elongation factor G: a GTP-driven motor of the ribosome. Essays Biochem. 35, 117-29
13. How can elongation factors EF-G and EF-Tu discriminate the functional state of the ribosome using the same binding site? FEBS Lett. 579, 5439-42
14. Ribosomal translocation: sparsomycin pushes the button. Curr. Biol. 13, R652-4