Oligomerization of the cysteinyl-rich oligopeptidase EP24.15 is triggered by S-glutathionylation
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
20/10/2012
20/10/2012
2008
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Resumo |
Thimet oligopeptidase (EC 3.4.24.15; 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 mu M. The in vitro 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-disulfide exchange. (c) 2007 Elsevier Inc. All rights reserved. |
Identificador |
FREE RADICAL BIOLOGY AND MEDICINE, v.44, n.6, p.1180-1190, 2008 0891-5849 http://producao.usp.br/handle/BDPI/28128 10.1016/j.freeradbiomed.2007.12.012 |
Idioma(s) |
eng |
Publicador |
ELSEVIER SCIENCE INC |
Relação |
Free Radical Biology and Medicine |
Direitos |
restrictedAccess Copyright ELSEVIER SCIENCE INC |
Palavras-Chave | #thimet oligopeptidase EP24.15 #S-glutathionylation #redox modulation #thiol-disulfide exchange #catalytic redox modulation #oxidative oligornerization #DISULFIDE-BOND FORMATION #PROTEIN-SULFENIC ACIDS #I ANTIGEN PRESENTATION #THIMET OLIGOPEPTIDASE #EC 3.4.24.15 #ENDOPEPTIDASE 24.15 #OXIDATIVE STRESS #REDOX REGULATION #METALLOENDOPEPTIDASE #CATALYSIS #Biochemistry & Molecular Biology #Endocrinology & Metabolism |
Tipo |
article original article publishedVersion |