PDZdomein

PDZ domain, known in Dutch as the PDZ-domein, is a modular protein interaction domain found in many signaling and scaffolding proteins. The name PDZ comes from the first three proteins in which the domain was identified: PSD-95, Dlg, and ZO-1.

Structurally, a PDZ domain comprises about 80–90 amino acids that fold into a conserved arrangement of a beta-sheet and an alpha-helix, forming a peptide-binding groove. This groove recognizes short C-terminal sequences of partner proteins, classifying binding motifs as class I, II, or III, though variations exist. In many proteins, multiple PDZ domains occur in tandem and can assemble signaling complexes by binding multiple ligands or through PDZ–PDZ interactions.

Function and role: PDZ domains act as scaffolds at the plasma membrane, organizing receptors, channels, transporters, and signaling enzymes in specialized membrane microdomains. They are especially prominent in neurons (synaptic scaffolds such as the PSD-95 family) and epithelial cells (tight junctions such as ZO proteins). By localizing components, PDZ domains regulate signaling strength, receptor trafficking, and the architecture of signaling networks.

Occurrence and significance: PDZ domains are found across eukaryotes and are encoded in hundreds of human proteins. Disruption of PDZ-mediated interactions has been linked to neurological disorders, cancer, and ciliopathies. PDZ domains are also used in research and biotechnology as modular binding units and as targets for strategies to disrupt protein interactions.