PDZ domain protein-protein interactions: a case study with PICK1.
Using PICK1 as an example this review highlights PDZ domains support a repertoire of protein-protein interactions that regulate the subcellular localisation and function of receptors, ion channels and enzymes. PICK1 is a 416 amino acid protein that contains a PDZ domain, a coiled-coil motif/arfaptin homology domain and an acidic c-terminal. Nearly all proteins thus far reported to interact with PICK1 do so via its single PDZ domain. PICK1 self-associates via its coiled-coil motif and together with its PDZ domain has potential to act as a scaffolding protein. This molecule was first identified as a protein interacting with Calpha-kinase (PICK1) and interacts with several members of the glutamate receptor family and receptor tyrosine kinases. The PDZ domain of PICK1 has since been shown to interact with a plethora of proteins including dopamine transporter, prolactin-releasing peptide receptor, ion channels BNaC1/ASIC and many more. The single PDZ domain of PICK1 interacts with a network of proteins that is pivotal in processes such as synaptic plasticity, development and neural guidance as well as many diseased states. The proteins that interact with PICK1 and the functional roles of its PDZ domain are discussed and illustrated are ways to regulate PDZ protein-protein interactions.
Dev
Kumlesh K
KK
Neurosciences, Department of Neurodegeneration, Novartis Institutes for BioMedical Research Basel, Novartis Pharma AG, WSJ-386.7.43, CH-4002 Basel, Switzerland. kumlesh_k.dev@novartis.com
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; C498297:PICk1 protein, human; C091822:Prkcabp protein, mouse