title: Solution structure of the second PDZ domain of the neuronal adaptor X11alpha and its interaction with the C-terminal peptide of the human copper chaperone for superoxide dismutase.
abstract: Protection against reactive oxygen species is provided by the copper containing enzyme superoxide dismutase 1 (SOD1). The copper chaperone CCS is responsible for copper insertion into apo-SOD1. This role is impaired by an interaction between the second PDZ domain (PDZ2alpha) of the neuronal adaptor protein X11alpha and the third domain of CCS (McLoughlin et al. (2001) J. Biol. Chem., 276, 9303-9307). The solution structure of the PDZ2alpha domain has been determined and the interaction with peptides derived from CCS has been explored. PDZ2alpha binds to the last four amino acids of the CCS protein (PAHL) with a dissociation constant of 91 +/- 2 microM. Peptide variants have been used to map the interaction areas on PDZ2alpha for each amino acid, showing an important role for the C-terminal leucine, in line with canonical PDZ-peptide interactions.
authors.affiliation: Leiden Institute of Chemistry, Leiden University, The Netherlands.
authors.forename: Aude E
authors.initials: AE
authors.lastname: Duquesne
authors.forename: Martina de
authors.initials: Md
authors.lastname: Ruijter
authors.forename: Jaap
authors.initials: J
authors.lastname: Brouwer
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Sander B
authors.initials: SB
authors.lastname: Nabuurs
authors.forename: Chris A E M
authors.initials: CA
authors.lastname: Spronk
authors.forename: Geerten W
authors.initials: GW
authors.lastname: Vuister
authors.forename: Marcellus
authors.initials: M
authors.lastname: Ubbink
authors.forename: Gerard W
authors.initials: GW
authors.lastname: Canters
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry*; D000595:Amino Acid Sequence; D001051:Apoenzymes / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000201:enzymology; D003001:Cloning, Molecular; D003300:Copper / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D012996:Solutions; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: C079091:APBA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D001051:Apoenzymes; C114678:CCS protein, human; D018076:DNA, Complementary; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C000606290:SOD1 protein, human; D012996:Solutions; D003300:Copper; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1