Details

Autor(en) / Beteiligte

• Moon, Jeong Chan
• Hah, Young-Sool
• Kim, Woe Yeon
• Jung, Bae Gyo
• Jang, Ho Hee
• Lee, Jung Ro
• Kim, Sun Young
• Lee, Young Mee
• Jeon, Min Gyu
• Kim, Choong Won
• Cho, Moo Je
• Lee, Sang Yeol

Titel

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

Ist Teil von

• The Journal of biological chemistry, 2005-08, Vol.280 (31), p.28775-28784

Ort / Verlag

United States: American Society for Biochemistry and Molecular Biology

Erscheinungsjahr

2005

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.