title: Reversal of 2-Cys peroxiredoxin oligomerization by sulfiredoxin.
abstract: Hydrogen peroxide (H(2)O(2)) regulates the structure and function of 2-Cys peroxiredoxins (Prxs). Upon oxidation by excess H(2)O(2), Prxs become overoxidized to a sulfinic acid of its peroxidatic cysteine residue, resulting in a structural change from a small oligomer with peroxidase function to a large oligomer with chaperone function. Then, sulfiredoxin (Srx) reduces the overoxidized Prxs by an ATP-dependent mechanism. Although Srx is known to repair the overoxidized forms of Prx, the role of Srx in the reversal of Prx oligomerization remains to be elucidated. Here we investigated whether Srx1 directly facilitates the dissociation of yeast Prx1 (YPrx1) from a high-molecular-weight (HMW) complex to a low-molecular-weight (LMW) complex in vitro. Srx1 reactivates the YPrx1 peroxidase activity that is inactivated by H(2)O(2), whereas it decreases the chaperone activity enhanced by H(2)O(2). We show that Srx1 dissociates the H(2)O(2)-induced HMW YPrx1 complex, and that the Srx1 Cys84 residue is critical for its dissociation. In contrast to wild-type Srx1, an inactive Srx1 mutant (Srx1-C84S) did not induce the reactivation of inactivated YPrx1 or dissociation of the HMW YPrx1 complex. We revealed that Srx1 interacts directly with YPrx1 in yeast cells using bimolecular fluorescence complementation. Taken together, these findings suggest that Srx1 regulates YPrx1 function and structure in yeast cells through a direct interaction.
authors: Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-799, Republic of Korea.
authors: Jeong Chan
authors: JC
authors: Moon
authors: Gyeong Mi
authors: GM
authors: Kim
authors: Eun-Kyung
authors: EK
authors: Kim
authors: Hae Na
authors: HN
authors: Lee
authors: Bin
authors: B
authors: Ha
authors: Sang Yeol
authors: SY
authors: Lee
authors: Ho Hee
authors: HH
authors: Jang
mesh_terms: D018832:Molecular Chaperones / Q000378:metabolism; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000378:metabolism*; D010544:Peroxidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins / Q000378:metabolism*; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014867:Water / Q000378:metabolism
chemical_list: D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D014867:Water; C410041:PRX1 protein, S cerevisiae; D010544:Peroxidases; D054464:Peroxiredoxins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C479426:SRX1 protein, S cerevisiae