title: Crystal structure of human DJ-1, a protein associated with early onset Parkinson's disease.
abstract: We report the crystal structure at 1.8-A resolution of human DJ-1, which has been linked to early onset Parkinson's disease. The monomer of DJ-1 contains the alpha/beta-fold that is conserved among members of the DJ-1/ThiJ/PfpI superfamily. However, the structure also contains an extra helix at the C terminus, which mediates a novel mode of dimerization for the DJ-1 proteins. A putative active site has been identified near the dimer interface, and the residues Cys-106, His-126, and Glu-18 may play important roles in the catalysis by this protein. Studies with the disease-causing L166P mutant suggest that the mutation has disrupted the C-terminal region and the dimerization of the protein. The DJ-1 proteins may function only as dimers. The Lys to Arg mutation at residue 130, the site of sumoylation of DJ-1, has minimal impact on the structure of the protein.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Tao
authors.forename: Liang
authors.initials: L
authors.lastname: Tong
mesh_terms: D017668:Age of Onset; D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D003461:Crystallography; D019281:Dimerization; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics*; D017354:Point Mutation; D000071617:Protein Deglycase DJ-1; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D025842:SUMO-1 Protein / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D025842:SUMO-1 Protein; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1