title: Oxidative stress-dependent structural and functional switching of a human 2-Cys peroxiredoxin isotype II that enhances HeLa cell resistance to H2O2-induced cell death.
abstract: Although biochemical properties of 2-Cys peroxiredoxins (Prxs) have been extensively studied, their real physiological functions in higher eukaryotic cells remain obscure and certainly warrant further study. Here we demonstrated that human (h) PrxII, a cytosolic isotype of human 2-Cys Prx, has dual functions as a peroxidase and a molecular chaperone, and that these different functions are closely associated with its adoption of distinct protein structures. Upon exposure to oxidative stress, hPrxII assumes a high molecular weight complex structure that has a highly efficient chaperone function. However, the subsequent removal of stressors induces the dissociation of this protein structure into low molecular weight proteins and triggers a chaperone-to-peroxidase functional switch. The formation of a high molecular weight hPrxII complex depends on the hyperoxidation of its N-terminal peroxidatic Cys residue as well as on its C-terminal domain, which contains a "YF motif" that is exclusively found in eukaryotic 2-Cys Prxs. A C-terminally truncated hPrxII exists as low and oligomeric protein species and does not respond to oxidative stress. Moreover, this C-terminal deletion of hPrxII converted it from an oxidation-sensitive to a hyperoxidation-resistant form of peroxidase. When functioning as a chaperone, hPrxII protects HeLa cells from H(2)O(2)-induced cell death, as measured by a terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay and fluorescence-activated cell sorting analysis.
authors.affiliation: Environmental Biotechnology National Core Research Center, Division of Applied Life Sciences (BK21 Program), Department of Biochemistry, College of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju 660-701, Korea.
authors.forename: Jeong Chan
authors.initials: JC
authors.lastname: Moon
authors.forename: Young-Sool
authors.initials: YS
authors.lastname: Hah
authors.forename: Woe Yeon
authors.initials: WY
authors.lastname: Kim
authors.forename: Bae Gyo
authors.initials: BG
authors.lastname: Jung
authors.forename: Ho Hee
authors.initials: HH
authors.lastname: Jang
authors.forename: Jung Ro
authors.initials: JR
authors.lastname: Lee
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Young Mee
authors.initials: YM
authors.lastname: Lee
authors.forename: Min Gyu
authors.initials: MG
authors.lastname: Jeon
authors.forename: Choong Won
authors.initials: CW
authors.lastname: Kim
authors.forename: Moo Je
authors.initials: MJ
authors.lastname: Cho
authors.forename: Sang Yeol
authors.initials: SY
authors.lastname: Lee
mesh_terms: D016923:Cell Death / Q000187:drug effects*; D003600:Cytosol / Q000201:enzymology; D004351:Drug Resistance; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D018832:Molecular Chaperones / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010544:Peroxidases / Q000378:metabolism*; D054464:Peroxiredoxins
chemical_list: D007527:Isoenzymes; D018832:Molecular Chaperones; D006861:Hydrogen Peroxide; D010544:Peroxidases; D054464:Peroxiredoxins