PROSITE documentation PDOC00273 [for PROSITE entry PS51722]

Translational (tr)-type guanine nucleotide-binding (G) domain signature and profile




Description

The P-loop (see <PDOC00017>) 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 [1]:

  • Prokaryotic initiation factor 2 (IF2) and the related eukaryotic initiation factor 5B (eIF5B), catalyze ribosomal subunit joining to form elongation- competent ribosomes [2,3].
  • Bacterial SelB and eukaryotic/archaeal γ subunit of initiation factor 2 (eIF-2γ), specifically recognize noncanonical tRNAs. SelB specifically recognizes selenocysteylated tRNA(Sec) and eIF-2γ initiator tRNA (Met-tRNA(i)) [4,5].
  • Bacterial elongation factor Tu (EF-Tu) and its archaeal and eukaryotic counterpart elongation factor 1 (EF-1 α), bring the aminoacyl-tRNA into the A site of the ribosome [6,7].
  • Bacterial peptide elongation factor G (EF-G) and its counterpart in Eukarya and Archaea, EF-2, catalyze the translocation step of translation [8,9].

The basic topology of the tr-type G domain consists of a six-stranded central β-sheet surrounded by five α-helices (see <PDB:4AC9>). Helices α2, α3 and α4 are on one side of the sheet, whereas α1 and α5 are on the other [5]. 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 γ-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 β- and γ-phosphates, and two are provided by the side chains of G1 and G2 threonines [3].

We developed both a pattern and a profile for the tr-type G domain. The pattern 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. The profile we developed covers the entire tr-type G domain.

Note:

The pattern does not detect the IF2/eIF5B subfamily.

Last update:

June 2014 / Text revised; profile added.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

G_TR_2, PS51722; Translational (tr)-type guanine nucleotide-binding (G) domain profile  (MATRIX)

G_TR_1, PS00301; Translational (tr)-type guanine nucleotide-binding (G) domain signature  (PATTERN)


References

1AuthorsLeipe D.D., Wolf Y.I., Koonin E.V., Aravind L.
TitleClassification and evolution of P-loop GTPases and related ATPases.
SourceJ. Mol. Biol. 317:41-72(2002).
PubMed ID11916378
DOI10.1006/jmbi.2001.5378

2AuthorsEiler D., Lin J., Simonetti A., Klaholz B.P., Steitz T.A.
TitleInitiation factor 2 crystal structure reveals a different domain organization from eukaryotic initiation factor 5B and mechanism among translational GTPases.
SourceProc. Natl. Acad. Sci. U.S.A. 110:15662-15667(2013).
PubMed ID24029018
DOI10.1073/pnas.1309360110

3AuthorsKuhle B., Ficner R.
TitleeIF5B employs a novel domain release mechanism to catalyze ribosomal subunit joining.
SourceEMBO J. 33:1177-1191(2014).
PubMed ID24686316
DOI10.1002/embj.201387344

4AuthorsKeeling P.J., Fast N.M., McFadden G.I.
TitleEvolutionary relationship between translation initiation factor eIF-2gamma and selenocysteine-specific elongation factor SELB: change of function in translation factors.
SourceJ. Mol. Evol. 47:649-655(1998).
PubMed ID9847405

5AuthorsLeibundgut M., Frick C., Thanbichler M., Boeck A., Ban N.
TitleSelenocysteine tRNA-specific elongation factor SelB is a structural chimaera of elongation and initiation factors.
SourceEMBO J. 24:11-22(2005).
PubMed ID15616587
DOI10.1038/sj.emboj.7600505

6AuthorsAEvarsson A.
TitleStructure-based sequence alignment of elongation factors Tu and G with related GTPases involved in translation.
SourceJ. Mol. Evol. 41:1096-1104(1995).
PubMed ID8587108

7AuthorsInagaki Y., Doolittle W.F., Baldauf S.L., Roger A.J.
TitleLateral transfer of an EF-1alpha gene: origin and evolution of the large subunit of ATP sulfurylase in eubacteria.
SourceCurr. Biol. 12:772-776(2002).
PubMed ID12007424

8AuthorsAl-Karadaghi S., AEvarsson A., Garber M., Zheltonosova J., Liljas A.
TitleThe structure of elongation factor G in complex with GDP: conformational flexibility and nucleotide exchange.
SourceStructure 4:555-565(1996).
PubMed ID8736554

9AuthorsMargus T., Remm M., Tenson T.
TitleA computational study of elongation factor G (EFG) duplicated genes: diverged nature underlying the innovation on the same structural template.
SourcePLoS ONE 6:E22789-E22789(2011).
PubMed ID21829651
DOI10.1371/journal.pone.0022789



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