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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Demasi, Marilene ; Piassa Filho, Gilberto M. ; Castro, Leandro M. ; Ferreira, Juliana C. ; Rioli, Vanessa ; Ferro, Emer S. [6]
Total Authors: 6
Document type: Journal article
Source: Free Radical Biology and Medicine; v. 44, n. 6, p. 1180-1190, Mar. 2008.
Field of knowledge: Biological Sciences - Morphology

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 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. (AU)

FAPESP's process: 04/04933-2 - Molecular cell biology of oligopeptidases
Grantee:Emer Suavinho Ferro
Support type: Research Projects - Thematic Grants
FAPESP's process: 06/06969-0 - Models for study in cell culture of 20S proteasomal modulators obtained from former in vitro screening
Grantee:Marilene Demasi
Support type: Regular Research Grants