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PDZ Domain

No Image PDZ domains contain ~80-90 residues that fold into a structure with a b-sandwich of 5-6 b-strands and two a-helices. The peptide ligand binds in a hydrophobic cleft composed of a b-strand (bB), an a-helix and a loop that binds the peptide carboxylate group. The peptide binds in an anti-parallel fashion to the bB strand, with the C-terminal residue occupying a hydrophobic pocket. PDZ heterodimers form a linear head-to-tail arrangement that involves recognition of an internal binding site on one of the partner proteins. The figure shows the 3rd PDZ domain of PSD-95 bound to a TKNYKQTSV peptide.

Structure Reference:
Doyle, DA. et al. (1996) Cell. 85(7): 1067-76. PDB: 1BE9.

Domain binding and function:
PDZ (postsynaptic density 95, PSD-85; discs large, Dlg; zonula occludens-1, ZO-1) domains are one of the most frequently encountered domains, consisting of approximately 90 residues long and identified as a region of sequence homology among a diverse list of signaling proteins.   PDZ domains can occur in one or multiple copies and are nearly always found in cytoplasmic proteins.  The PDZ domain consists of six β strands and two α-helices, compactly arranged in a globular structure.   Similar in ways to PTB and PH domains, PDZ domains lack common peptide binding specificities and have the ability to interact with peptides and lipids.   There are currently four different classes of PDZ interactions: recognition of carboxyl-terminal motifs in peptides, recognition of internal motifs in peptides, PDZ-PDZ dimerization, and recognition of lipids.   Furthermore, PDZ domains that interact with C-terminal peptides can be divided into three separate classes according to their specificity.
Examples of Proteins: 
PDZ domain protein
Binding partner Binding site Class Type
Post-synaptic Density protein 95 (PSD-95) NMDA receptor B via PDZ1 and PDZ2 of PSD-95 IESDV-COOHClass I: X-S or T-X-V
Post-synaptic Density protein 95 (PSD-95) Kvl1.4 (Shaker-type K+ channel) via PDZ1 and PDZ2 of PSD-95 VETDV-COOHClass I: X-S or T-X-V
Post-synaptic Density protein 95 (PSD-95) neural Nitric Oxide Synthase (nNOS) via PDZ2 PDZ/PDZ interaction

β2 ľadrenergic receptor

Class I: X-S or T-X-L

Neurexin, Syndecan

Class II: X-Ψ-X-Ψ

Melatonin Receptor

Class III: X-D or E-X-Ψ

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