InterPro domain: IPR000795

Translational GTPases (trGTPases) are a family of proteins in which GTPase activity is stimulated by the large ribosomal subunit. This family includes translation initiation, elongation, and release factors and contains four subfamilies that are widespread, if not ubiquitous, in all three superkingdoms [ 1 ]. The trGTPase family members include bacteria elongation factors, EFTu, EFG, and the initiation factor, IF2, and their archaeal homologues, the EF1, EF2, aeIF5b and aeIF2. They all contain two homologous N-terminal domains: a GTPase or G-domain, followed by an OB-domain. These translational proteins' G-domains are both structurally and functionally related to a larger family of GTPase G proteins [ 2 ]. This entry represents the G-domain of the trGTPases.

The basic topology of the tr-type G domain consists of a six-stranded central beta-sheet surrounded by five alpha-helices. Helices alpha2, alpha3 and alpha4 are on one side of the sheet, whereas alpha1 and alpha5 are on the other [ 2 ]. GTP is bound by the CTF-type G domain in a way common for G domains involving five conserved sequence motifs termed G1-G5. The base is in contact with the NKxD (G4) and SAx (G5) motifs, and the phosphates of the nucleotide are stabilized by main- and side-chain interactions with the P loop GxxxxGKT (G1). The most severe conformational changes are observed for the two switch regions which contain the xT/Sx (G2) and DxxG (G3) motifs that function as sensors for the presence of the gamma-phosphate. A Mg(2+) ion is coordinated by six oxygen ligands with octahedral coordination geometry; two of the ligands are water molecules, two come from the beta- and gamma- phosphates, and two are provided by the side chains of G1 and G2 threonines [ 3 ].

In both prokaryotes and eukaryotes, there are three distinct types of elongation factors, EF-1alpha (EF-Tu), which binds GTP and an aminoacyl-tRNA and delivers the latter to the A site of ribosomes; EF-1beta (EF-Ts), which interacts with EF-1a/EF-Tu to displace GDP and thus allows theregeneration of GTP-EF-1a; and EF-2 (EF-G), which binds GTP and peptidyl-tRNA and translocates the latter from the A site to the P site. In EF-1-alpha, a specific region has been shown [ 4 ] to be involved in a conformational change mediated by the hydrolysis of GTP to GDP. This region is conserved in both EF-1alpha/EF-Tu as well as EF-2/EF-G and thus seems typical for GTP-dependent proteins which bind non-initiator tRNAs to the ribosome. The GTP-binding protein synthesis factor family also includes the eukaryotic peptide chain release factor GTP-binding subunits [ 5 ] and prokaryotic peptide chain release factor 3 (RF-3) [ 6 ]; the prokaryotic GTP-binding protein lepA and its homologue in yeast (GUF1) and Caenorhabditis elegans (ZK1236.1); yeast HBS1 [ 7 ]; rat statin S1 [ 8 ]; and the prokaryotic selenocysteine-specific elongation factor selB [ 9 ].

1. Classification and evolution of P-loop GTPases and related ATPases. J. Mol. Biol. 317, 41-72
2. Selenocysteine tRNA-specific elongation factor SelB is a structural chimaera of elongation and initiation factors. EMBO J. 24, 11-22
3. eIF5B employs a novel domain release mechanism to catalyze ribosomal subunit joining. EMBO J. 33, 1177-91
4. A conserved amino acid sequence around Arg-68 of Artemia elongation factor 1 alpha is involved in the binding of guanine nucleotides and aminoacyl transfer RNAs. Biochimie 69, 983-9
5. The products of the SUP45 (eRF1) and SUP35 genes interact to mediate translation termination in Saccharomyces cerevisiae. EMBO J. 14, 4365-73
6. Function of polypeptide chain release factor RF-3 in Escherichia coli. RF-3 action in termination is predominantly at UGA-containing stop signals. J. Biol. Chem. 270, 10595-600
7. The translation machinery and 70 kd heat shock protein cooperate in protein synthesis. Cell 71, 97-105
8. Isolation and characterization of the rat chromosomal gene for a polypeptide (pS1) antigenically related to statin. J. Biol. Chem. 266, 10429-37
9. Identification of a novel translation factor necessary for the incorporation of selenocysteine into protein. Nature 342, 453-6