JCI - PDZ domains: fundamental building blocks in the organization of protein complexes at the plasma membrane

PDZ domains: fundamental building blocks in the organization of protein complexes at the plasma membrane

Alan S. Fanning, James Melvin Anderson

J Clin Invest. 1999; 103(6):767–772 doi:10.1172/JCI6509

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Figure 3

Schematic diagram of InaD and NHERF, illustrating the protein–protein interactions mediated by these two PDZ proteins. (a) InaD binds to the G protein (G_qα)–linked receptor rhodopsin (Rh), the light-activated cation channels TRP and TRPL, phospholipase C-β (PLC), and protein kinase C (PKC) via PDZ domains. Calmodulin binds to the region between PDZ1 and PDZ2. A higher-order structure is organized at the plasma membrane by homomeric and heteromeric binding between PDZ domains 3 and 4. Reproduced, with permission, from ref. 9. (b) The β₂-adrenergic receptor binds to the first PDZ domain of NHERF, and the Na⁺/H⁺ exchanger NHE-3 binds to a region adjacent to and including the second PDZ domain. Ezrin binds to a domain in the COOH-terminus of NHERF, linking the protein complex to the actin cytoskeleton and protein kinase A (PKA-II). Both PKA-II and the β₂-adrenergic receptor regulate the activity of NHE-3.