Organization of signaling complexes by PDZ-domain scaffold proteins

Transduction of biological signals from receptors at the plasma membrane to their targets in cytoplasm and nucleus relies on specific protein-protein interactions. A common strategy used by cells is to organize proteins in the same signaling cascade into large molecular weight, multiprotein complexes. PDZ domain proteins have been shown to play important roles in assembling various signaling complexes. Here, we first present biophysical basis of the advantages of organizing proteins in a signaling cascade into a clustered multiprotein complex. We then discuss the structure, ligand binding, and function of PDZ domains in organizing synaptic signaling complexes.