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PROSITE documentation PDOC50106 [for PROSITE entry PS50106]

PDZ domain profile





Description

PDZ domains (also called Discs-large homologous regions (DHR) or GLGF) are conserved structural elements of 80 to 100 amino acids that were originally identified in the post-synaptic density protein PSD-95, the Drosophila tumor suppressor discs-large, and the tight-junction protein ZO-1. PDZ domains occur as single or, more frequently, as multiple tandemly repeated copies in a large and diverse set of proteins from all eukaryotes [1,2]. The presence of one or two copies of PDZ domains in some bacteria may be explained by horizontal gene transfer [3].

Eukaryotic PDZ domains are multifunctional protein-protein interaction modules that are involved in the clustering of signaling molecules and play important role in organizing protein networks on membranes. In many cases, PDZ domains bind to a signature motif ([FYST]-X-[FVA]) occurring at the very C-terminus of target proteins. PDZ domains are also able to form heterodimers, and to interact with internal peptide fragments of target proteins [1,2,4]. It has been proposed that bacterial PDZ domains also possess C-terminal polypeptide binding functions [3].

PDZ domains are compact globular domains that were originally called GLGF as Gly-Leu-Gly-Phe is a relatively conserved element of their sequences [1]. Resolution of crystal and solution structures of PDZ domains with and without ligands has revealed that the PDZ domain contains six β-strands and two α-helices [5,6,7,8]. The C-terminal motif of target proteins has been shown to bind in an anti-parallel fashion to a groove formed by the principal α-helix and the second β-strand of the PDZ domains [5,8]. The binding site involved in the heterodimerization of some PDZ domains is situated opposite this canonical peptide binding groove. It is an about 30 residue C-terminal extension of the PDZ domain, which forms a β-hairpin finger. The first strand of the β-hairpin finger mimics a canonical C-terminal peptide ligand, inserting into the peptide binding groove of the PDZ domain from the partner protein [7,8]. It has been proposed that PDZ domains may bind in a general fashion to non-terminal sequences, possibly those with β-finger-type structures, regardless of whether or not they are found downstream of other PDZ domains [9].

Some proteins known to contain a PDZ domain are listed below:

  • Eukaryotic membrane associated guanylate kinases (MAGUKs).
  • Mammalian amyloid β A4 precursor protein-binding family A proteins, putative function in synaptic vesicle exocytosis by binding to Munc18-1, an essential component of the synaptic vesicle exocytotic machinery.
  • Mammalian neuronal nitric oxide synthase (nNOS).
  • Interleukin-16, the only known secreted member of the PDZ protein family.
  • Vertebrate LIM-kinases (LIMK), which display serine/threonine-specific phosphorylation of myelin basic protein and histone in vitro.
  • Drosophila and vertebrate dishevelled (Dsh and Dvl), proteins that play a key role in the transduction of the Wg/Wnt signal from the cell surface to the nucleus.
  • Drosophila InaD, a photoreceptor scaffolding protein that assembles multiple signal transducing proteins at the membrane via its 5 PDZ domains.
  • Bacillus subtilis stage IV sporulation B protein (spOIVB).
  • Bacterial gspC proteins, involved in protein export via type II secretion systems.
  • Bacterial periplasmic serine proteases high-temperature requirement A (htrA) and tail-specific protease (tsp).
  • Escherichia coli and Haemophilus influenzae hypothetical protein YaeL, probably associated with the cytoplasmic membrane.

A profile was developed that covers the minimal PDZ domain and thus lacks about 30 C-terminal residues (which form the β finger involved in PDZ-PDZ interactions).

Last update:

December 2001 / First entry.

Technical section

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

PDZ, PS50106; PDZ domain profile  (MATRIX)


References

1AuthorsPonting C.P., Phillips C., Davies K.E., Blake D.J.
TitlePDZ domains: targeting signalling molecules to sub-membranous sites.
SourceBioEssays 19:469-479(1997).
PubMed ID9204764

2AuthorsRanganathan R., Ross E.M.
TitlePDZ domain proteins: scaffolds for signaling complexes.
SourceCurr. Biol. 7:R770-R773(1997).
PubMed ID9382826

3AuthorsPonting C.P.
TitleEvidence for PDZ domains in bacteria, yeast, and plants.
SourceProtein Sci. 6:464-468(1997).
PubMed ID9041651

4AuthorsFuh G., Pisabarro M.T., Li Y., Quan C., Lasky L.A., Sidhu S.S.
TitleAnalysis of PDZ domain-ligand interactions using carboxyl-terminal phage display.
SourceJ. Biol. Chem. 275:21486-21491(2000).
PubMed ID10887205
DOI275/28/21486

5AuthorsDoyle D.A., Lee A., Lewis J., Kim E., Sheng M., MacKinnon R.
TitleCrystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ.
SourceCell 85:1067-1076(1996).
PubMed ID8674113

6AuthorsMorais Cabral J.H., Petosa C., Sutcliffe M.J., Raza S., Byron O., Poy F., Marfatia S.M., Chishti A.H., Liddington R.C.
SourceNature 382:649-652(1996).

7AuthorsHillier B.J., Christopherson K.S., Prehoda K.E., Bredt D.S., Lim W.A.
TitleUnexpected modes of PDZ domain scaffolding revealed by structure of nNOS-syntrophin complex.
SourceScience 284:812-815(1999).
PubMed ID10221915

8AuthorsTochio H., Zhang Q., Mandal P., Li M., Zhang M.
TitleSolution structure of the extended neuronal nitric oxide synthase PDZ domain complexed with an associated peptide.
SourceNat. Struct. Biol. 6:417-421(1999).
PubMed ID10331866
DOI10.1038/8216

9AuthorsOschkinat H.
TitleA new type of PDZ domain recognition.
SourceNat. Struct. Biol. 6:408-410(1999).
PubMed ID10331862
DOI10.1038/8203



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