PROSITE documentation PDOC00362

Dynamin-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.

Members of the dynamin GTPase family appear to be ubiquitous. They catalyze diverse membrane remodelling events in endocytosis, cell division, and plastid maintenance. Their functional versatility also extends to other core cellular processes, such as maintenance of cell shape or centrosome cohesion. Members of the dynamin family are characterized by their common structure and by conserved sequences in the GTP-binding domain. The minimal distinguishing architectural features that are common to all dynamins and are distinct from other GTPases are the structure of the large GTPase domain (~280 amino acids) and the presence of two additional domains: the middle domain and the GTPase effector domain (GED) (see <PDOC51388>), which are involved in oligomerization and regulation of the GTPase activity. In many dynamin family members, the basic set of domains is supplemented by targeting domains, such as: pleckstrin-homology (PH) domain (see <PDOC50003>), proline-rich domains (PRDs), or by sequences that target dynamins to specific organelles, such as mitochondria and chloroplasts [1,2,3].

The dynamin-type G domain consists of a central eight-stranded β-sheet surrounded by seven α helices and two one-turn helices (see <PDB:4H1U>). It contains the five canonical guanine nucleotide binding motifs (G1-5). The P-loop (G1) motif (GxxxxGKS/T) is also present in ATPases (Walker A motif) and functions as a coordinator of the phosphate groups of the bound nucleotide. A conserved threonine in switch-I (G2) and the conserved residues DxxG of switch-II (G3) are involved in Mg(2+) binding and GTP hydrolysis. The nucleotide binding affinity of dynamins is typically low, with specificity for GTP provided by the mostly conserved N/TKxD motif (G4). The G5 or G-cap motif is involved in binding the ribose moiety [4,5,6].

Some proteins containing a dynamin-type G domain are listed below [2,3]:

  • Animal dynamin, the prototype for this family. The role of dynamin in endocytosis is well established. Additional roles were proposed in vesicle budding from the trans-Golgi network (TGN) and the budding of caveolae from the plasma membrane [4].
  • Vetebrate Mx proteins, a group of interferon (IFN)-induced GTPases involved in the control of intracellular pathogens [6,7].
  • Eukaryotic Drp1 (Dnm1 in yeast) mediates mitochondrial and peroxisomal fission.
  • Eukaryotic Eps15 homology (EH)-domain-containing proteins (EHDs), ATPases implicated in clathrin-independent endocytosis and recycling from endosomes. The dynamin-type G domains of EHDs bind to adenine rather than to guanine nucleotide [8,9].
  • Yeast to human OPA1/Mgm1 proteins. They are found between the inner and outer mitochondrial membranes and are involved in mitochondrial fusion.
  • Yeast to human mitofusin/fuzzy onions 1 (Fzo1) proteins, involved in mitochondrial dynamics [10,11].
  • Yeast vacuolar protein sorting-associated protein 1 (Vps1), involved in vesicle trafficking from the Golgi.
  • Escherichia coli clamp-binding protein CrfC (or Yjda), important for the colocalization of sister nascent DNA strands after replication fork passage during DNA replication, and for positioning and subsequent partitioning of sister chromosomes [12]
  • Nostoc punctiforme bacterial dynamin-like protein (BDLP) [13,14],

The signature pattern that we developed for the dynamin-type G domain is based on a highly conserved region downstream of the ATP/GTP-binding motif 'A' (P-loop) (see <PDOC00017>). We also developed a profile that covers the entire domain.

Last update:

May 2014 / Text revised; profile added.

Technical section

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

G_DYNAMIN_2, PS51718; Dynamin-type guanine nucleotide-binding (G) domain profile  (MATRIX)

G_DYNAMIN_1, PS00410; Dynamin-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

2Authorsvan der Bliek A.M.
TitleFunctional diversity in the dynamin family.
SourceTrends Cell Biol. 9:96-102(1999).
PubMed ID10201074

3AuthorsPraefcke G.J.K., McMahon H.T.
TitleThe dynamin superfamily: universal membrane tubulation and fission molecules?
SourceNat. Rev. Mol. Cell Biol. 5:133-147(2004).
PubMed ID15040446
DOI10.1038/nrm1313

4AuthorsFord M.G.J., Jenni S., Nunnari J.
TitleThe crystal structure of dynamin.
SourceNature 477:561-566(2011).
PubMed ID21927001
DOI10.1038/nature10441

5AuthorsWenger J., Klinglmayr E., Froehlich C., Eibl C., Gimeno A., Hessenberger M., Puehringer S., Daumke O., Goettig P.
TitleFunctional mapping of human dynamin-1-like GTPase domain based on x-ray structure analyses.
SourcePLoS ONE 8:E71835-E71835(2013).
PubMed ID23977156
DOI10.1371/journal.pone.0071835

6AuthorsGao S., von der Malsburg A., Dick A., Faelber K., Schroeder G.F., Haller O., Kochs G., Daumke O.
TitleStructure of myxovirus resistance protein a reveals intra- and intermolecular domain interactions required for the antiviral function.
SourceImmunity 35:514-525(2011).
PubMed ID21962493
DOI10.1016/j.immuni.2011.07.012

7AuthorsVerhelst J., Hulpiau P., Saelens X.
TitleMx proteins: antiviral gatekeepers that restrain the uninvited.
SourceMicrobiol. Mol. Biol. Rev. 77:551-566(2013).
PubMed ID24296571
DOI10.1128/MMBR.00024-13

8AuthorsDaumke O., Lundmark R., Vallis Y., Martens S., Butler P.J., McMahon H.T.
TitleArchitectural and mechanistic insights into an EHD ATPase involved in membrane remodelling.
SourceNature 449:923-927(2007).
PubMed ID17914359
DOI10.1038/nature06173

9AuthorsShah C., Hegde B.G., Moren B., Behrmann E., Mielke T., Moenke G., Spahn C.M.T., Lundmark R., Daumke O., Langen R.
TitleStructural insights into membrane interaction and caveolar targeting of dynamin-like EHD2.
SourceStructure 22:409-420(2014).
PubMed ID24508342
DOI10.1016/j.str.2013.12.015

10AuthorsKurashima K., Chae M., Inoue H., Hatakeyama S., Tanaka S.
TitleA uvs-5 strain is deficient for a mitofusin gene homologue, fzo1, involved in maintenance of long life span in Neurospora crassa.
SourceEukaryot. Cell 12:233-243(2013).
PubMed ID23223037
DOI10.1128/EC.00226-12

11AuthorsCohen M.M., Amiott E.A., Day A.R., Leboucher G.P., Pryce E.N., Glickman M.H., McCaffery J.M., Shaw J.M., Weissman A.M.
TitleSequential requirements for the GTPase domain of the mitofusin Fzo1 and the ubiquitin ligase SCFMdm30 in mitochondrial outer membrane fusion.
SourceJ. Cell Sci. 124:1403-1410(2011).
PubMed ID21502136
DOI10.1242/jcs.079293

12AuthorsOzaki S., Matsuda Y., Keyamura K., Kawakami H., Noguchi Y., Kasho K., Nagata K., Masuda T., Sakiyama Y., Katayama T.
TitleA replicase clamp-binding dynamin-like protein promotes colocalization of nascent DNA strands and equipartitioning of chromosomes in E. coli.
SourceCell Rep. 4:985-995(2013).
PubMed ID23994470
DOI10.1016/j.celrep.2013.07.040

13AuthorsLow H.H., Loewe J.
TitleDynamin architecture--from monomer to polymer.
SourceCurr. Opin. Struct. Biol. 20:791-798(2010).
PubMed ID20970992
DOI10.1016/j.sbi.2010.09.011

14AuthorsLow H.H., Sachse C., Amos L.A., Loewe J.
TitleStructure of a bacterial dynamin-like protein lipid tube provides a mechanism for assembly and membrane curving.
SourceCell 139:1342-1352(2009).
PubMed ID20064379
DOI10.1016/j.cell.2009.11.003



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