PDZ2

PDZ2 is the second PDZ domain found in several multi-domain scaffold proteins, most notably the postsynaptic density protein PSD-95 (also known as DLG4). PDZ2 is a modular protein interaction domain of about 80–90 amino acids that participates in recognizing and binding short C-terminal peptide motifs of partner proteins, enabling assembly of signaling complexes at cellular membranes.

Structure and binding properties: PDZ2 adopts the canonical PDZ fold, consisting of a conserved groove formed by a combination of beta strands and alpha helices. A GLGF loop contributes to defining the ligand-binding pocket, which interacts with the carboxyl terminus of target proteins. PDZ domains typically recognize short C-terminal motifs, with preferences that can vary among PDZ domains. In PSD-95, PDZ2 participates in binding to the C-termini of various postsynaptic partners, including transmembrane receptor subunits and auxiliary proteins such as TARPs (stargazin family), helping to organize receptor complexes at synapses.

Functional role: By engaging multiple ligands, PDZ2 contributes to the clustering and stabilization of synaptic receptors and signaling molecules at the postsynaptic density. This organization supports efficient synaptic transmission and plasticity, linking receptors to downstream signaling pathways and cytoskeletal elements through the broader scaffold network.

Distribution and significance: PDZ2 is one of several PDZ domains within PSD-95 family proteins and is found in other eukaryotic scaffold proteins as well. Its study provides insight into modular protein-protein interactions that underlie membrane organization, signaling specificity, and, when perturbed, potential links to neurological dysfunction.