Crystal structure of a PDZ domain

• Published in: Nature (London) 1996-08, Vol.382 (6592), p.649-652
• Main Authors: Cabral, João H. Morais, Petosa, Carlo, Sutcliffe, Michael J, Raza, Sami, Byron, Olwyn, Poy, Florence, Marfatia, Shirin M, Chishti, Athar H, Liddington, Robert C
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Binding and carrier proteins; Binding Sites; Biochemistry; Biological and medical sciences; Crystallography, X-Ray; Crystals; Drosophila; Fundamental and applied biological sciences. Psychology; Genes; Genes, Tumor Suppressor; Humanities and Social Sciences; Humans; Ions; letter; Membrane Proteins; Models, Molecular; Molecular Sequence Data; multidisciplinary; Nitric oxide; Proteins; Proteins - chemistry; Proteins - genetics; Recombinant Proteins - chemistry; Science; Science (multidisciplinary); Sequence Homology, Amino Acid
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/382649a0

PDZ domains (also known as DHR domains or GLGF repeats) are ~90-residue repeats found in a number of proteins implicated in ion-channel and receptor clustering, and the linking of receptors to effector enzymes1. PDZ domains are protein-recognition modules; some recognize proteins containing the consensus carboxy-terminal tripeptide motif S/TXV with high specificity 2–4 . Other PDZ domains form homotypic dimers: the PDZ domain of the neuronal enzyme nitric oxide synthase binds to the PDZ domain of PSD-95, an interaction that has been implicated in its synaptic association 5 . Here we report the crystal structure of the third PDZ domain of the human homologue of the Drosophila discs-large tumour-suppressor gene product, DlgA. It consists of a five-stranded antiparallel β-barrel flanked by three α-helices. A groove runs over the surface of the domain, ending in a conserved hydrophobic pocket and a buried arginine; we suggest that this is the binding site for the C-terminal peptide.