PROSITE documentation PDOC51831 [for PROSITE entry PS51831]

HD, HD-GYP and HD-related output (HDOD) domains profiles





Description

The HD domain, named after the conserved doublet of predicted catalytic residues, is found in a wide range of bacterial, archaeal and eukaryotic proteins. It defines a superfamily of phosphohydrolases that can catalyze both metal-dependent and -independent phosphomonoesterase and phosphodiesterase reactions for a broad range of substrates [1,2]:

  • Bacterial dGTPase.
  • Bacterial polyA polymerases.
  • Bacterial CCA-adding enzymes, catalyze the addition and repair of the essential 3'-terminal CCA sequence in tRNAs without using a nucleic acid template.
  • Bacterial uridylyl transferases (GlnD).
  • Bacterial stringent-response guanosine polyphosphate [ppgpp(p)] hydrolase/ synthetase (SpoT/RelA).
  • Fungal cyanamide lyase.

The HD-domain proteins appear to be involved in nucleic acid and nucleotide metabolism, signal transduction and possibly other functions. They are diverse in terms of both domain architecture and phylogenetic distribution; each of the completely sequenced genomes encodes more than one version of this domain.

The HD domain is composed of a bundle of α helices with a 5-helix core (see <PDB:2PAR>). Although all HD domains share key design features, a striking diversity of catalytic centres have been identified, containing no metal, mono-, bi- or trinuclear metal binding sites [2,3].

A distinct version of this domain, HD-GYP, contains a number of additional highly conserved residues. The spectrum of the domains that are associated with HD-GYP in multidomain proteins suggests that it is probably involved in signal transduction. The HD-GYP family of HD proteins so far is lacking in archaea and eukaryotes. The HD-GYP domain is likely to be a conserved scaffold whose main role is to allow protein-protein interactions with partner GGDEF domains (see <PDOC50887>) while achieving (a) different function(s) through diversification of the active-site cavity and the N-terminal regulatory domains [4,5,6].

  • Xanthomonas campestris RpfG, a multi-phenotype protein involved in virulence, motility and biofilm regulation. It functions as cyclic di- 3',5'-GMP (c-di-GMP) degrading phosphodiesterase.
  • Persephonella marina PmGH, a cyclic di-3',5'-GMP (c-di-GMP) phosphodiesterase.
  • Bdellovibrio bacteriovorus Bd1817, a catalytically inactive protein.
  • Pseudomonas aeruginosa PA4781 protein, a phosphodiesterase involved in cyclic di-3',5'-GMP (c-di-GMP) degradation.
  • Pseudomonas aeruginosa PA4108 protein,
  • Vibrio cholerae VCA0861, contains tandem HD and HD-GYP domains [6].

In addition to the HD domain 5-helix core, the HD-GYP domain contains two extra C-terminal helices (see <PDB:4MCW>) [3,5,7,8].

The HD-related output domain (HDOD) is a protein domain of unknown function. Proteins containing the HDOD are widespread in diverse bacteria; it can be present as a stand-alone domain, and also associated with other domains, such as response regulatory (RR) (see <PDOC50110>), GGDEF (see <PDOC50887>), and EAL (see <PDOC50883>), suggesting a role in regulation and signaling [9,10]:

  • Campylobacter jejuni virulence factor CJ048, a stand-alone HDOD containing protein required for motility and involved in colonization of the chick gastrointestinal tract.
  • Xanthomonas campestris pv. campestris (Xcc) GsmR (general stress and motility regulator), plays a role in the general stress response of Xcc and is involved in the expression of genes responsible for flagellum synthesis. It has a RR domain at the N-terminus and a C-terminal HDOD.
  • Xanthomonas campestris pv. campestris (Xcc) HdpA, contains a HDOD at the N- terminus and a GGDEF domain at the C-terminus.
  • Xanthomonas campestris pv. campestris (Xcc) HdpB, a stand-alone HDOD containing protein.

The HDOD domain folds into a complex arrangement of α helices (see <PDB:1VQR>) [11].

The profiles we developed cover respectively the core HD domain and the entire HD-GYP and HDOD domains.

Last update:

June 2017 / Profile added.

Technical section

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

HD, PS51831; HD domain profile  (MATRIX)

HDOD, PS51833; HD-related output (HDOD) domain profile  (MATRIX)

HD_GYP, PS51832; HD-GYP domain profile  (MATRIX)


References

1AuthorsAravind L., Koonin E.V.
TitleThe HD domain defines a new superfamily of metal-dependent phosphohydrolases.
SourceTrends Biochem. Sci. 23:469-472(1998).
PubMed ID9868367

2AuthorsZimmerman M.D., Proudfoot M., Yakunin A., Minor W.
TitleStructural insight into the mechanism of substrate specificity and catalytic activity of an HD-domain phosphohydrolase: the 5'-deoxyribonucleotidase YfbR from Escherichia coli.
SourceJ. Mol. Biol. 378:215-226(2008).
PubMed ID18353368
DOI10.1016/j.jmb.2008.02.036

3AuthorsBellini D., Caly D.L., McCarthy Y., Bumann M., An S.-Q., Dow J.M., Ryan R.P., Walsh M.A.
TitleCrystal structure of an HD-GYP domain cyclic-di-GMP phosphodiesterase reveals an enzyme with a novel trinuclear catalytic iron centre.
SourceMol. Microbiol. 91:26-38(2014).
PubMed ID24176013
DOI10.1111/mmi.12447

4AuthorsGalperin M.Y., Natale D.A., Aravind L., Koonin E.V.
TitleA specialized version of the HD hydrolase domain implicated in signal transduction.
SourceJ. Mol. Microbiol. Biotechnol. 1:303-305(1999).
PubMed ID10943560

5AuthorsRinaldo S., Paiardini A., Stelitano V., Brunotti P., Cervoni L., Fernicola S., Protano C., Vitali M., Cutruzzola F., Giardina G.
TitleStructural basis of functional diversification of the HD-GYP domain revealed by the Pseudomonas aeruginosa PA4781 protein, which displays an unselective bimetallic binding site.
SourceJ. Bacteriol. 197:1525-1535(2015).
PubMed ID25691523
DOI10.1128/JB.02606-14

6AuthorsMiner K.D., Klose K.E., Kurtz D.M. Jr.
TitleAn HD-GYP cyclic di-guanosine monophosphate phosphodiesterase with a non-heme diiron-carboxylate active site.
SourceBiochemistry 52:5329-5331(2013).
PubMed ID23883166
DOI10.1021/bi4009215

7AuthorsLovering A.L., Capeness M.J., Lambert C., Hobley L., Sockett R.E.
TitleThe structure of an unconventional HD-GYP protein from Bdellovibrio reveals the roles of conserved residues in this class of cyclic-di-GMP phosphodiesterases.
SourceMBio 2:0-0(2011).
PubMed ID21990613
DOI10.1128/mBio.00163-11

8AuthorsWigren E., Liang Z.X., Roemling U.
TitleFinally! The structural secrets of a HD-GYP phosphodiesterase revealed.
SourceMol. Microbiol. 91:1-5(2014).
PubMed ID24236493
DOI10.1111/mmi.12463

9AuthorsLiu Y.-F., Liao C.-T., Song W.-L., Hsu P.-C., Du S.-C., Lo H.-H., Hsiao Y.-M.
TitleGsmR, a response regulator with an HD-related output domain in Xanthomonas campestris, is positively controlled by Clp and is involved in the expression of genes responsible for flagellum synthesis.
SourceFEBS J. 280:199-213(2013).
PubMed ID23137357
DOI10.1111/febs.12061

10AuthorsLee H.-M., Liao C.-T., Chiang Y.-C., Chang Y.-Y., Yeh Y.-T., Du S.-C., Hsiao Y.-M.
TitleCharacterization of genes encoding proteins containing HD-related output domain in Xanthomonas campestris pv. campestris.
SourceAntonie Van Leeuwenhoek 109:509-522(2016).
PubMed ID26821378
DOI10.1007/s10482-016-0656-y

11AuthorsXu Q., Schwarzenbacher R., McMullan D., Abdubek P., Agarwalla S., Ambing E., Axelrod H., Biorac T., Canaves J.M., Chiu H.-J., Deacon A.M., DiDonato M., Elsliger M.-A., Godzik A., Grittini C., Grzechnik S.K., Hale J., Hampton E., Han G.W., Haugen J., Hornsby M., Jaroszewski L., Klock H.E., Koesema E., Kreusch A., Kuhn P., Lesley S.A., Miller M.D., Moy K., Nigoghossian E., Paulsen J., Quijano K., Reyes R., Rife C., Spraggon G., Stevens R.C., van den Bedem H., Velasquez J., White A., Wolf G., Hodgson K.O., Wooley J., Wilson I.A.
TitleCrystal structure of virulence factor CJ0248 from Campylobacter jejuni at 2.25 A resolution reveals a new fold.
SourceProteins 62:292-296(2006).
PubMed ID16287129
DOI10.1002/prot.20611



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