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, Young-Sool Hah, Woe Yeon Kim, Bae Gyo Jung, Ho Hee Jang, Jung Ro Lee, Sun Young Kim, Young Mee Lee, Min Gyu Jeon, Choong Won Kim, Moo Je Cho, Sang Yeol Lee
2005 Journal of Biological Chemistry  
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,
more » ... idative 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-toperoxidase 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 nickend labeling assay and fluorescence-activated cell sorting analysis.
doi:10.1074/jbc.m505362200 pmid:15941719 fatcat:72ewjcwmjnctzh47ttgxfrsivm