PDZ DOMAINS - TARGETING SIGNALING MOLECULES TO SUB-MEMBRANOUS SITES

PDZ (also called DHR or GLGF) domains are found in diverse membrane-as sociated proteins including members of the MAGUK family of guanylate k inase homologues, several protein phosphatases and kinases, neuronal n itric oxide synthase, and several dystrophin-associated proteins, coll ectively known as syntrophins, Many PDZ domain-containing proteins app ear to be localised to highly specialised submembranous sites, suggest ing their participation in cellular junction formation, receptor or ch annel clustering, and intracellular signalling events. PDZ domains ol several MAGUKs interact with the C-terminal polypeptides of a subset o f NMDA receptor subunits and/or with Shaker-type K+ channels. Other PD Z domains have been shown to bind similar ligands of other transmembra ne receptors, Recently, the crystal structures of PDZ domains, with an d without ligand, have been determined. These demonstrate the mode of ligand-binding and the structural bases for sequence conservation amon g diverse PDZ domains.