PDZ domains are abundant protein interaction modules and typically recognize a short motif at the C terminus of their ligands, with a few residues in the motif endowing the binding specificity. The sequence-based rules, however, cannot fully account for the specificity between the vast number of PDZ domains and ligands in the cell. Plexins are transmembrane receptors that regulate processes suc...

PDZ domain is one of the abundant modular domains that recognize short peptide sequences to mediate protein-protein interactions. To decipher the binding specificity of PDZ domain, we analyzed the interactions between 11 mouse PDZ domains and 217 [corrected] peptides using a method called MIEC-SVM, which energetically characterizes the domain-peptide interaction using molecular interaction ener...

PDZ domains are protein-protein interaction modules sharing the same structural arrangement. To discern whether they display common features in their unfolding/misfolding behaviour we have analyzed in this work the unfolding thermodynamics, together with the misfolding kinetics, of the PDZ fold using three archetypical examples: the second and third PDZ domains of the PSD95 protein and the Erbi...

Over 250 PDZ (PSD95/Dlg/ZO-1) domain-containing proteins have been described in the human proteome. As many of these possess multiple PDZ domains, the potential combinations of associations with proteins that possess PBMs (PDZ-binding motifs) are vast. However, PDZ domain recognition is a highly specific process, and much less promiscuous than originally thought. Furthermore, a large number of ...

Several hundred PDZ (postsynaptic density-95, Drosophila disks-large, ZO-1) domain-containing proteins have been identified in the human genome. PDZ domains play a critical role in organization and function of cellular signaling pathways. Thus, small molecule inhibitors of PDZ domain association with their targets have wide potential applications as research and therapeutic agents. PDZ domains ...

PTEN (phosphatase and tensin homolog deleted on chromosome 10) and MAST2 (microtubule-associated serine and threonine kinase 2) interact with each other through the PDZ domain of MAST2 (MAST2-PDZ) and the carboxyl-terminal (C-terminal) PDZ domain-binding site (PDZ-BS) of PTEN. These two proteins function as negative regulators of cell survival pathways, and silencing of either one promotes neur...

The PDZ domain is a protein-protein interaction module that interacts with a C-terminal short peptide motif in its binding partners. A variety of methods have been used to study PDZ domain interactions. This chapter details the two methods most commonly used in the analysis of PDZ interactions: yeast two-hybrid and coimmunoprecipitation assays. In addition, we discuss the features that must be ...

PDZ domains mediate protein-protein interactions at specialized subcellular sites, such as epithelial cell tight junctions and neuronal post-synaptic densities. Because most PDZ domains bind extreme carboxyl-terminal sequences, the phage display method has not been amenable to the study of PDZ domain binding specificities. For the first time, we demonstrate the functional display of a peptide l...

PICK1 is a peripheral membrane protein conserved from Caenorhabditis elegans to the human. It is expressed in many tissues with high levels in brain and testis. Inside cells, PICK1 is localized at the perinuclear region as well as specialized structures such as synapses of neurons. PICK1 contains a PDZ domain and a BAR domain. The PDZ domain of PICK1 binds to a large number of membrane proteins...

PDZ domain proteins use the PDZ domain binding motif to bind to the C-terminal sequence of membrane proteins to help scaffold them and spatially organize the components of the intracellular signaling machinery. We have identified a sequence at the C terminus of a G protein-coupled receptor, the PrRP receptor, that shares similarities with the C-terminal sequence of alpha-amino-3-hydroxy-5-methy...