Roles of distinct cysteine residues in S-nitrosylation and dimerization of DJ-1.
A significant proportion of early onset parkinsonism is inherited as an autosomal-recessive trait (AR-EP). DJ-1 was identified as one of the causative genes for AR-EP (PARK7), and DJ-1 protein has been implicated in oxidative stress response through oxidation of one of the three cysteine residues (i.e., Cys106). However, the individual roles of these cysteine residues remained unclear. We show by a systematic mutagenesis analysis that Cys46 and Cys53 of DJ-1, but not Cys106, are susceptible to S-nitrosylation in vitro as well as in cultured cells. Furthermore, alanine substitution of Cys46 diminished dimerization of DJ-1, a fundamental feature of this protein. These results indicate that distinct cysteine residues of DJ-1 harbor differential roles in relation to its structure and function.
Ito
Genta
G
The Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
Ariga
Hiroyoshi
H
Nakagawa
Yasuhito
Y
Iwatsubo
Takeshi
T
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003545:Cysteine / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation / Q000235:genetics; D009584:Nitrogen / Q000737:chemistry*; D015513:Oncogene Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D000071617:Protein Deglycase DJ-1
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D003545:Cysteine; D009584:Nitrogen