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Crystal structure of a PDZ domain

Nature volume 382, pages 649–652 (1996)Cite this article

Abstract

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 specificity2–4. 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 association5. 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.

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Authors and Affiliations

  1. Department of Biochemistry, University of Leicester, Leicester, LE1 7RH, UK

    João H. Morais Cabral, Carlo Petosa, Olwyn Byron & Robert C. Liddington

  2. NCMH, University of Leicester, Leicester, LE1 7RH, UK

    Olwyn Byron

  3. Department of Chemistry, University of Leicester, Leicester, LE1 7RH, UK

    Michael J. Sutcliffe & Sami Raza

  4. Dana–Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts, 02115, USA

    Florence Poy

  5. Laboratory of Tumor Cell Biology, St Elizabeth's Medical Center, Tufts University School of Medicine, 736 Cambridge Street, Boston, Massachusetts, 02135, USA

    Shirin M. Marfatia & Athar H. Chishti

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  1. João H. Morais Cabral
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Cabral, J., Petosa, C., Sutcliffe, M. et al. Crystal structure of a PDZ domain. Nature 382, 649–652 (1996). https://doi.org/10.1038/382649a0

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