Conserved Site

Tr-type G domain, conserved site (IPR031157)

Short name: G_TR_CS

Description

The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

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 [PMID: 11916378]:

  • Prokaryotic initiation factor 2 (IF2) and the related eukaryotic initiation factor 5B (eIF5B), catalyze ribosomal subunit joining to form elongation- competent ribosomes [PMID: 24029018, PMID: 24686316].
  • Bacterial SelB and eukaryotic/archaeal gamma subunit of initiation factor 2 (eIF-2gamma), specifically recognise noncanonical tRNAs. SelB specifically recognises selenocysteylated tRNA(Sec) and eIF-2gamma initiator tRNA (Met-tRNA(i)) [PMID: 9847405, PMID: 15616587].
  • Bacterial elongation factor Tu (EF-Tu) and its archaeal and eukaryotic counterpart elongation factor 1 (EF-1 alpha), bring the aminoacyl-tRNA into the A site of the ribosome [PMID: 8587108, PMID: 12007424].
  • Bacterial peptide elongation factor G (EF-G) and its counterpart in Eukarya and Archaea, EF-2, catalyse the translocation step of translation [PMID: 8736554, PMID: 21829651].

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 [PMID: 15616587]. 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 stabilised 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.

This entry represents a conserved site in the tr-type G domain. It is on a G2-containing region that has been shown to be involved in a conformational change mediated by the hydrolysis of GTP to GDP.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns