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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 - PubMed

  • ️Sat Jan 01 2005

. 2005 Aug 5;280(31):28775-84.

doi: 10.1074/jbc.M505362200. Epub 2005 Jun 7.

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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

Jeong Chan Moon et al. J Biol Chem. 2005.

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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.

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