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| PROSITE documentation PDOC50106 [for PROSITE entry PS50106] |
PDZ domain profile
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.
PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Ponting C.P., Phillips C., Davies K.E., Blake D.J. |
| Title | PDZ domains: targeting signalling molecules to sub-membranous sites. | |
| Source | BioEssays 19:469-479(1997). | |
| PubMed ID | 9204764 |
| 2 | Authors | Ranganathan R., Ross E.M. |
| Title | PDZ domain proteins: scaffolds for signaling complexes. | |
| Source | Curr. Biol. 7:R770-R773(1997). | |
| PubMed ID | 9382826 |
| 3 | Authors | Ponting C.P. |
| Title | Evidence for PDZ domains in bacteria, yeast, and plants. | |
| Source | Protein Sci. 6:464-468(1997). | |
| PubMed ID | 9041651 |
| 4 | Authors | Fuh G., Pisabarro M.T., Li Y., Quan C., Lasky L.A., Sidhu S.S. |
| Title | Analysis of PDZ domain-ligand interactions using carboxyl-terminal phage display. | |
| Source | J. Biol. Chem. 275:21486-21491(2000). | |
| PubMed ID | 10887205 | |
| DOI | 275/28/21486 |
| 5 | Authors | Doyle D.A., Lee A., Lewis J., Kim E., Sheng M., MacKinnon R. |
| Title | Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ. | |
| Source | Cell 85:1067-1076(1996). | |
| PubMed ID | 8674113 |
| 6 | Authors | Morais Cabral J.H., Petosa C., Sutcliffe M.J., Raza S., Byron O., Poy F., Marfatia S.M., Chishti A.H., Liddington R.C. |
| Source | Nature 382:649-652(1996). |
| 7 | Authors | Hillier B.J., Christopherson K.S., Prehoda K.E., Bredt D.S., Lim W.A. |
| Title | Unexpected modes of PDZ domain scaffolding revealed by structure of nNOS-syntrophin complex. | |
| Source | Science 284:812-815(1999). | |
| PubMed ID | 10221915 |
| 8 | Authors | Tochio H., Zhang Q., Mandal P., Li M., Zhang M. |
| Title | Solution structure of the extended neuronal nitric oxide synthase PDZ domain complexed with an associated peptide. | |
| Source | Nat. Struct. Biol. 6:417-421(1999). | |
| PubMed ID | 10331866 | |
| DOI | 10.1038/8216 |
| 9 | Authors | Oschkinat H. |
| Title | A new type of PDZ domain recognition. | |
| Source | Nat. Struct. Biol. 6:408-410(1999). | |
| PubMed ID | 10331862 | |
| DOI | 10.1038/8203 |
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