A PDZ domain is a part of a protein which can interact with other proteins. It is a modular protein interaction domain that binds sequence-specifically to short peptides within other proteins. Such specific binding sites called PDZ- binding motif. These binding sites are often located at the C -terminal end of a protein, but may also be located within a protein, for example in other PDZ domains.
Protein complexes formed by PDZ domains are involved in signal transduction of cells up to the establishment and maintenance of cell polarity.
PDZ domains were observed and described in 1991 for the first time. The first proteins in which PDZ domains were found were the synaptic protein PSD95/SAP90 (PSD stands for Post synaptic density ), the septate junction protein Discs large from Drosophila melanogaster and the tight junction protein zonula occludentes -1. Because of these three proteins, the PDZ domain has received its name. Names not so frequently used denominated DHR ( Dlg homologous region) or GLGF ( a relatively well conserved tetrapeptide in these domains).
Design and function
PDZ domains consist of approximately 90 amino acids and have a globular shape. The three-dimensional structure of different PDZ domains has now been solved and published by X-ray crystal structure analysis.
Proteins containing PDZ domains are usually so-called " protein scaffold " that is, scaffold proteins, which form the basis for the assembly of large protein complexes to specific subcellular compartments. The PDZ domains mediate here the direct interaction between the proteins. Up to 13 PDZ domains may be included in a protein.
The first identified and most common by far the function of PDZ domains is to recognize and interact with specific C -terminal motifs of partner proteins. The last and third to last amino acid forms for the specificity of the interaction to be primarily important so that based on these sequences, the PDZ domains were divided into three classes. Furthermore, since some examples of mediated PDZ domain interactions were detected with non -C -terminal motifs. Thus, some proteins form internal binding sites for PDZ domains that present the consensus sequence in a β - hairpin loop structure and thus mimic a C -terminus. Such a structure also exists in certain PDZ domains, so here interact with PDZ PDZ domains, a so-called " Head to Tail oligomerization ".
PDZ domains are found in various proteins, bacteria, yeasts, plants, insects and vertebrates. In humans, more than 240 proteins have been discovered, which comprise this domain. In general, these are cytoplasmic proteins. Better known examples include PSD -95, a member of the MAGUK family of proteins important for the establishment of synapses of neurons, nNOS, neuronal nitric oxide synthase, Harmonin, a scaffolding protein function in sensory cells and hHtrA, a bifunctional protein, and as a protease chaperone acts.