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 .
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 .
PDZ domains are compact globular domains that were originally called GLGF as
Gly-Leu-Gly-Phe is a relatively conserved element of their sequences .
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 .
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
- 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
- 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
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