Oligomerization of the cysteinyl-rich oligopeptidase EP24.15 is triggered by S-glutathionylation

资源类型:pdf 资源大小:100.00KB 文档分类: 上传者:丁香


  • 未找到相关文档


【作者】 Marilene Demasi  Gilberto M. Piassa Filho  Le  ro M. Castro  Juliana C. Ferreira  Vanessa Rioli  Emer S. Ferro 

【关键词】Thimet oligopeptidase EP24.15  S-glutathionylation  Redox modulation  Thiol– disulfide exchange  Catalytic redox modulation  Oxidative oligomerization 


【摘要】Thimet oligopeptidase (EC; EP24.15) is a thiol-rich metallopeptidase ubiquitously distributed in mammalian tissues and involved in oligopeptide metabolism both within and outside cells. Fifteen Cys residues are present in the rat EP24.15 protein, seven are solvent accessible, and two are found inside the catalytic site cleft; no intraprotein disulfide is described. In the present investigation, we show that mammalian immunoprecipitated EP24.15 is S-glutathionylated. In vitro EP24.15 S-glutathionylation was demonstrated by the incubation of bacterial recombinant EP24.15 with oxidized glutathione concentration as low as 10&#xa0;&#x3bc;M. The <i>in vitro</i> S-glutathionylation of EP24.15 was responsible for its oxidative oligomerization to dimer and trimer complexes. EP24.15 immunoprecipitated from cells submitted to oxidative challenge showed increased trimeric forms and decreased S-glutathionylation compared to immunoprecipitated protein from control cells. Our present data also show that EP24.15 maximal enzymatic activity is maintained by partial S-glutathionylation, a mechanism that apparently regulates the protein oligomerization. Present results raise the possibility of an unconventional property of protein S-glutathionylation, inducing oligomerization by interprotein thiol&#x2013;disulfide exchange.

【刊名】Free Radical Biology and Medicine