Crystal structure of a PDZ domain

Morais Cabral, Joao H.
Petosa, Carlo
Sutcliffe, Michael J.
Raza, Sami
Byron, Olwyn
Poy, Florence
Marfatia, Shirin M.
Chishti, Athar H.
Liddington, Robert C.

(Cabral, Petosa, Byron, Liddington) Departments of Biochemistry, (Byron) NCMH and (Sutcliffe, Raza) Chemistry, University of Leicester, Leicester LE1 7RH, UK.
(Poy) Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
(Marfatia, Chishti) Laboratory of Tumor Cell Biology, St Elizabeth's Medical Center, Tufts University School of Medicine, 736 Cambridge Street, Boston, Massachusetts 02135, USA.

Nature 382(6592):p 649-652, August 15, 1996.

PDZ domains (also known as DHR domains or GLGF repeats) are approximately 90-residue repeats found in a number of proteins implicated in ion-channel and receptor clustering, and the linking of receptors to effector enzymes . PDZ domains are protein-recognition modules; some recognize proteins containing the consensus carboxy-terminal tripeptide motif S/TXV with high specificity . 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 . 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 beta-barrel flanked by three alpha-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.