PDZ domain (PDZ)

The PDZ domain is a common structural protein domain of approximately 80–90 amino acids found in a diverse set of signaling proteins across bacteria, yeast, plants, viruses, and animals[1][4][3]. PDZ domains act as scaffolding modules that anchor membrane proteins, particularly receptors and ion channels, to the cytoskeleton and to each other, facilitating the formation and organization of signaling complexes at specific subcellular locations[1][5][7]. They typically recognize and bind short C-terminal motifs of partner proteins, but can also engage internal motifs and lipids, thus regulating protein localization, signal transduction, cell polarity, and cellular communication[3][4][5][8]. The term PDZ derives from the initials of the first proteins discovered with this domain: post-synaptic density protein 95 (PSD-95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (ZO-1)[1][3][4]. PDZ domains are highly conserved structurally, consisting of a β-barrel formed from 5–6 β-strands and 1–2 α-helices, forming a groove for peptide or protein binding[4][3][5]. Due to their pivotal role in a wide range of cellular processes and diseases including cancer and neurodegeneration, they are considered attractive but challenging therapeutic targets, with ongoing research into small molecule and peptide modulators aimed at disrupting or stabilizing PDZ-mediated interactions[4][3][7][8].

Other names

DHR domainGLGF domain

Scaffold modulation, Disruption or stabilization of protein-protein interactions