PDZinteracting

PDZinteracting refers to proteins or protein interactions that are mediated by PDZ domains, a widespread family of protein interaction modules found in signaling and scaffolding proteins. PDZ domains recognize short C-terminal sequences on partner proteins, known as PDZ-binding motifs, enabling specific and often multivalent associations that help organize protein complexes at membranes and within cellular compartments.

PDZ domains are typically about 80 to 90 amino acids long and fold into a compact structure that presents a binding groove for the C-terminus of target proteins. PDZ-binding motifs are categorized by motif classes, most commonly Class I (-X-S/T-X-Φ), Class II (-Φ-X-Φ), and Class III (-D/E-X-Φ), where Φ denotes a hydrophobic residue. The interaction is influenced by the exact motif, the PDZ domain’s amino acid composition, and sometimes by phosphorylation or other post-translational modifications that modulate affinity. Many PDZ interactions are multivalent, involving tandem PDZ domains or networks of PDZ-containing proteins, which can stabilize large signaling assemblies.

Biological roles of PDZinteracting proteins are diverse. They contribute to synaptic organization by clustering receptors and channels, regulate receptor trafficking and localization, and support epithelial cell polarity and tight junction formation. Well-known examples include PSD-95, which scaffolds NMDA receptors and signaling enzymes at glutamatergic synapses, and ZO-1, which links claudins to the cytoskeleton at tight junctions. PDZinteracting interactions are dynamic and can be regulated by phosphorylation, alternative splicing, and competitive binding, allowing rapid remodeling of signaling complexes in response to cellular cues.

The study of PDZinteracting proteins informs neuroscience, cell polarity, and membrane trafficking, and PDZ-targeted strategies are explored to modulate signaling in disease contexts.