PDZ domain
A PDZ domain is a part of a protein that 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 are called PDZ binding motifs . These binding sites are often at the C-terminal end of a protein, but can also be located within a protein, for example in other PDZ domains.
Protein complexes formed by PDZ domains are involved in signal transmission from cells to the establishment and maintenance of cell polarity .
history
PDZ domains were observed and described for the first time in 1991. The first proteins in which PDZ domains were found were the synaptic protein P SD95 / SAP90 (PSD stands for Post synaptic density ), the septate junction protein D iscs large from Drosophila melanogaster and the tight junction protein Z onula occludens 1. It is from these three proteins that the PDZ domain got its name. Designations that are no longer used so frequently are also DHR ( Dlg homologous region ) or GLGF (a relatively well conserved tetrapeptide in these domains).
Layout and function
PDZ domains consist of about 90 amino acids and have a globular shape. The three-dimensional structure of different PDZ domains has since been clarified and published by means of X-ray crystal structure analysis.
Proteins that contain PDZ domains, are usually so-called "scaffold proteins", ie, scaffold proteins , which form the basis for the organization of larger protein complexes to specific subcellular compartments form. The PDZ domains mediate the direct interaction between the proteins. A protein can contain up to 13 PDZ domains.
| PDZ domain | Consensus binding sequence | Ligand |
|---|---|---|
| Class I. | -X- S / T -X- L / V -COOH | |
| Syntrophin | -E- S -L- V | Na + channel |
| PSD-95 (PDZ-1 & -2) | -E- T -D- V | K + channel |
| NHERF (PDZ-1) | -D- S -S- L | Adrenoceptor |
| Class II | -X- Φ -X- Φ -COOH | |
| hCASK | -E- Y -Y- V | Neurexin |
| Erythrocyte p55 | -E- F -Y- I | Glycophorin C |
| CASK | -E- Y -F- I | SynCAM |
| Class III / Others | ||
| Mint-1 | -D- H -W- C | Ca 2+ channel |
| nNOS | -V- D -S- V | Melatonin receptor |
The first identified and by far the most common function of PDZ domains is the recognition and interaction with specific C-terminal motifs of partner proteins. The last and the third from last amino acid seem to be mainly decisive for the specificity of the interaction, so that the PDZ domains were divided into three classes on the basis of these sequences. Furthermore, some examples of interactions with non-C-terminal motifs mediated by PDZ domains have now also been discovered. For example, some proteins form internal binding sites for PDZ domains, which present the consensus sequence in a β- hairpin loop structure and thus imitate a C-terminus. Such a structure also exists in certain PDZ domains, so that PDZ interacts with PDZ domains, a so-called “head to tail oligomerization”.
distribution
PDZ domains have been found in various proteins from bacteria , yeast , plants , insects and vertebrates . To date, over 240 proteins have been discovered in humans that contain this domain. Usually these are cytoplasmic proteins. Well-known examples are PSD-95 , a member of the MAGUK protein family that is important for building synapses in nerve cells , nNOS , a neuronal NO synthase, harmonine , a scaffold protein that functions in sensory cells, and hHtrA, a human serine protease .
credentials
- ↑ T. Biederer et al .: SynCAM, a synaptic adhesion molecule that drives synapse assembly. In: Science. 297, 2002, pp. 1525-1531. PMID 12202822 .
literature
- C. Nourry, SG Grant, JP Borg: PDZ domain proteins: plug and play! In: Sci.STKE. 179, 2003, p. Re7.
- M. Sheng, C. Sala: PDZ domains and the organization of supramolecular complexes. In: Annu.Rev.Neurosci. 24, 2001, pp. 1-29.