PDZ domains: fundamental building blocks in the organization of protein complexes at the plasma membrane
J. Clin. Invest. Alan S. Fanning, et al. 103:767 doi:10.1172/JCI6509 [
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Figure 3Schematic diagram of InaD and NHERF, illustrating the protein–protein interactions mediated by these two PDZ proteins. (
a) InaD binds to the G protein (
Gqα)–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 β
2-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 β
2-adrenergic receptor regulate the activity of NHE-3.