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.
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.
Duquesne
Aude E
AE
Leiden Institute of Chemistry, Leiden University, The Netherlands.
Ruijter
Martina de
Md
Brouwer
Jaap
J
Drijfhout
Jan W
JW
Nabuurs
Sander B
SB
Spronk
Chris A E M
CA
Vuister
Geerten W
GW
Ubbink
Marcellus
M
Canters
Gerard W
GW
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
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