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.
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.
Moon
Jeong Chan
JC
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.
Hah
Young-Sool
YS
Kim
Woe Yeon
WY
Jung
Bae Gyo
BG
Jang
Ho Hee
HH
Lee
Jung Ro
JR
Kim
Sun Young
SY
Lee
Young Mee
YM
Jeon
Min Gyu
MG
Kim
Choong Won
CW
Cho
Moo Je
MJ
Lee
Sang Yeol
SY
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
D007527:Isoenzymes; D018832:Molecular Chaperones; D006861:Hydrogen Peroxide; D010544:Peroxidases; D054464:Peroxiredoxins