 PDZ Domain | |
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Structure:
 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.
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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.
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Examples of Proteins:
| PDZ domain protein |
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Binding partner |
Binding site | Class Type
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| Post-synaptic Density protein 95 (PSD-95) |  |
NMDA receptor B via PDZ1 and PDZ2 of PSD-95 |
IESDV-COOH | Class I: X-S or T-X-V
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| Post-synaptic Density protein 95 (PSD-95) | |
Kvl1.4 (Shaker-type K+ channel) via PDZ1 and PDZ2 of PSD-95 |
VETDV-COOH | Class I: X-S or T-X-V
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| Post-synaptic Density protein 95 (PSD-95) | |
neural Nitric Oxide Synthase (nNOS) via PDZ2 |
PDZ/PDZ interaction |
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NHERF or EBP50
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β2 –adrenergic receptor
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| Class I: X-S or T-X-L
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CASK
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Neurexin, Syndecan
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| Class II: X-Ψ-X-Ψ
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nNOS
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Melatonin Receptor
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| Class III: X-D or E-X-Ψ
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Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
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