Polymerization of Oxidized DJ-1 via Noncovalent and Covalent Binding: Significance of Disulfide Bond Formation

Mayuka Kobayashi, Kana Muramatsu, Takamitsu Haruyama, Haruka Uesugi, Ai Kikuchi, Hiroki Konno, Noriko Noguchi, Yoshiro Saito

Research output: Contribution to journalArticlepeer-review

Abstract

The reactive cysteine residue at position 106 (Cys106) of DJ-1 is preferentially oxidized under oxidative stress, generating oxidized DJ-1 (oxDJ-1). Oxidation of Cys106 to sulfinic acid changes the biologic action of DJ-1 and increases its cytoprotective properties. The similar activation step is known in peroxiredoxins (Prxs), in which oxidation of reactive Cys to sulfinic acid induces polymerization of Prxs and changes its enzyme characteristic from peroxidase to molecular chaperone. In the present study, oxDJ-1 was prepared and its polymerization and related amino acid residues were investigated. We found that oxDJ-1 formed a characteristic polymer with disulfide bonds and with noncovalent and covalent binding other than disulfide. The physiological concentration of glutathione resolved the polymer form of oxDJ-1, and glutathionylation of other two Cys residues, such as Cys 46 and 53, was detected. Mutant analysis indicated the necessity not only of Cys106 but also of Cys46 for the polymer formation. The cellular experiment demonstrated that the electrophilic quinone treatment induced a high-molecular-weight complex containing oxDJ-1. Dynamic polymerization of oxDJ-1 with a ring and a stacked structure was observed by an atomic force microscope. Collectively, these results clearly demonstrated the characteristic polymer formation of oxDJ-1 with a disulfide bond and noncovalent and covalent binding other than disulfide, which might be related to the biologic function of oxDJ-1.

Original languageEnglish
Pages (from-to)9603-9614
Number of pages12
JournalACS Omega
Volume4
Issue number6
DOIs
Publication statusPublished - 2019 Jun 3

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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