PROSITE documentation PDOC00017

ATP/GTP-binding site motif A (P-loop)




Description

From sequence comparisons and crystallographic data analysis it has been shown [1,2,3,4,5,6] that an appreciable proportion of proteins that bind ATP or GTP share a number of more or less conserved sequence motifs. The best conserved of these motifs is a glycine-rich region, which typically forms a flexible loop between a β-strand and an α-helix. This loop interacts with one of the phosphate groups of the nucleotide. This sequence motif is generally referred to as the 'A' consensus sequence [1] or the 'P-loop' [5].

There are numerous ATP- or GTP-binding proteins in which the P-loop is found. We list below a number of protein families for which the relevance of the presence of such motif has been noted:

  • ATP synthase α and β subunits (see <PDOC00137>).
  • Myosin heavy chains.
  • Kinesin heavy chains and kinesin-like proteins (see <PDOC00343>).
  • Dynamins and dynamin-like proteins (see <PDOC00362>).
  • Guanylate kinase (see <PDOC00670>).
  • Thymidine kinase (see <PDOC00524>).
  • Thymidylate kinase (see <PDOC01034>).
  • Shikimate kinase (see <PDOC00868>).
  • Nitrogenase iron protein family (nifH/chlL) (see <PDOC00580>).
  • ATP-binding proteins involved in 'active transport' (ABC transporters) [7] (see <PDOC00185>).
  • DNA and RNA helicases [8,9,10].
  • GTP-binding elongation factors (EF-Tu, EF-1α, EF-G, EF-2, etc.).
  • Ras family of GTP-binding proteins (Ras, Rho, Rab, Ral, Ypt1, SEC4, etc.).
  • Nuclear protein ran (see <PDOC00859>).
  • ADP-ribosylation factors family (see <PDOC00781>).
  • Bacterial dnaA protein (see <PDOC00771>).
  • Bacterial recA protein (see <PDOC00131>).
  • Bacterial recF protein (see <PDOC00539>).
  • Guanine nucleotide-binding proteins α subunits (Gi, Gs, Gt, G0, etc.).
  • DNA mismatch repair proteins mutS family (See <PDOC00388>).
  • Bacterial type II secretion system protein E (see <PDOC00567>).

Not all ATP- or GTP-binding proteins are picked-up by this motif. A number of proteins escape detection because the structure of their ATP-binding site is completely different from that of the P-loop. Examples of such proteins are the E1-E2 ATPases or the glycolytic kinases. In other ATP- or GTP-binding proteins the flexible loop exists in a slightly different form; this is the case for tubulins or protein kinases. A special mention must be reserved for adenylate kinase, in which there is a single deviation from the P-loop pattern: in the last position Gly is found instead of Ser or Thr.

Expert(s) to contact by email:

Koonin E.V.

Last update:

July 1999 / Text revised.

Technical section

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

ATP_GTP_A, PS00017; ATP/GTP-binding site motif A (P-loop)  (PATTERN with a high probability of occurrence!)


References

1AuthorsWalker J.E., Saraste M., Runswick M.J., Gay N.J.
TitleDistantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold.
SourceEMBO J. 1:945-951(1982).
PubMed ID6329717

2AuthorsMoller W., Amons R.
TitlePhosphate-binding sequences in nucleotide-binding proteins.
SourceFEBS Lett. 186:1-7(1985).
PubMed ID2989003

3AuthorsFry D.C., Kuby S.A., Mildvan A.S.
TitleATP-binding site of adenylate kinase: mechanistic implications of its homology with ras-encoded p21, F1-ATPase, and other nucleotide-binding proteins.
SourceProc. Natl. Acad. Sci. U.S.A. 83:907-911(1986).
PubMed ID2869483

4AuthorsDever T.E., Glynias M.J., Merrick W.C.
TitleGTP-binding domain: three consensus sequence elements with distinct spacing.
SourceProc. Natl. Acad. Sci. U.S.A. 84:1814-1818(1987).
PubMed ID3104905

5AuthorsSaraste M., Sibbald P.R., Wittinghofer A.
TitleThe P-loop -- a common motif in ATP- and GTP-binding proteins.
SourceTrends Biochem. Sci. 15:430-434(1990).
PubMed ID2126155

6AuthorsKoonin E.V.
TitleA superfamily of ATPases with diverse functions containing either classical or deviant ATP-binding motif.
SourceJ. Mol. Biol. 229:1165-1174(1993).
PubMed ID8445645

7AuthorsHiggins C.F., Hyde S.C., Mimmack M.M., Gileadi U., Gill D.R., Gallagher M.P.
TitleBinding protein-dependent transport systems.
SourceJ. Bioenerg. Biomembr. 22:571-592(1990).
PubMed ID2229036

8AuthorsHodgman T.C.
TitleA new superfamily of replicative proteins.
SourceNature 333:22-23(1988) and Nature 333:578-578(1988) (Errata).
PubMed ID3362205
DOI10.1038/333022b0

9AuthorsLinder P., Lasko P.F., Ashburner M., Leroy P., Nielsen P.J., Nishi K., Schnier J., Slonimski P.P.
TitleBirth of the D-E-A-D box.
SourceNature 337:121-122(1989).
PubMed ID2563148
DOI10.1038/337121a0

10AuthorsGorbalenya A.E., Koonin E.V., Donchenko A.P., Blinov V.M.
SourceNucleic Acids Res. 17:4713-4730(1989).



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