Ito Genta, Ariga Hiroyoshi, Nakagawa Yasuhito, Iwatsubo Takeshi
The Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
Biochem Biophys Res Commun. 2006 Jan 13;339(2):667-72. doi: 10.1016/j.bbrc.2005.11.058. Epub 2005 Nov 18.
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.
相当一部分早发性帕金森病是作为常染色体隐性性状（AR-EP）遗传的。DJ-1被鉴定为AR-EP（PARK7）的致病基因之一，并且DJ-1蛋白通过三个半胱氨酸残基之一（即Cys106）的氧化参与氧化应激反应。然而，这些半胱氨酸残基的各自作用仍不清楚。我们通过系统的诱变分析表明，DJ-1的Cys46和Cys53而非Cys106在体外以及培养细胞中易于发生S-亚硝基化。此外，Cys46的丙氨酸取代减少了DJ-1的二聚化，这是该蛋白的一个基本特征。这些结果表明，DJ-1不同的半胱氨酸残基在其结构和功能方面具有不同的作用。
