Plasticity of PDZ domains in ligand recognition and signaling

The PDZ domain is a protein–protein interacting module that plays an important role in the organization of signaling complexes. The recognition of short intrinsically disordered C‐terminal peptide motifs is the archetypical PDZ function, but the functional repertoire of this versatile module also includes recognition of internal peptide sequences, dimerization and phospholipid binding. The PDZ function can be tuned by various means such as allosteric effects, changes of physiological buffer conditions and phosphorylation of PDZ domains and/or ligands, which poses PDZ domains as dynamic regulators of cell signaling. This review is focused on the plasticity of the PDZ interactions.