Two Endoplasmic Reticulum PDI Peroxidases Increase the Efficiency of the Use of Peroxide during Disulfide Bond Formation

被引：216

作者：

Nguyen, Van Dat ^{[1
]}

Saaranen, Mirva J. ^{[1
]}

Karala, Anna-Riikka ^{[1
]}

Lappi, Anna-Kaisa ^{[1
]}

Wang, Lei ^{[2
]}

Raykhel, Irina B. ^{[1
]}

Alanen, Heli I. ^{[1
]}

Salo, Kirsi E. H. ^{[1
]}

Wang, Chih-chen ^{[2
]}

Ruddock, Lloyd W. ^{[1
]}

机构：

[1] Univ Oulu, Dept Biochem, FIN-90570 Oulu, Finland

[2] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2011年 / 406卷 / 03期

基金：

芬兰科学院;

关键词：

oxidative protein folding; protein disulfide isomerase; hydrogen peroxide; glutathione peroxidase; thioredoxin fold; GLUTATHIONE-PEROXIDASE; PEROXIREDOXIN-IV; GENERATING DISULFIDES; OXIDATIVE STRESS; HUMAN-CELLS; PROTEIN; ISOMERASES; PATHWAY; DEGRADATION; MECHANISM;

D O I：

10.1016/j.jmb.2010.12.039

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Disulfide bond formation in the endoplasmic reticulum by the sulfhydryl oxidase Ero1 family is thought to be accompanied by the concomitant formation of hydrogen peroxide. Since secretory cells can make substantial amounts of proteins that contain disulfide bonds, the production of this reactive oxygen species could have potentially lethal consequences. Here, we show that two human proteins, GPx7 and GPx8, labeled as secreted glutathione peroxidases, are actually endoplasmic reticulum-resident protein disulfide isomerase peroxidases. In vitro, the addition of GPx7 or GPx8 to a folding protein along with protein disulfide isomerase and peroxide enables the efficient oxidative refolding of a reduced denatured protein. Furthermore, both GPx7 and GPx8 interact with Ero1 alpha in vivo, and GPx7 significantly increases oxygen consumption by Ero1 alpha in vitro. Hence, GPx7 and GPx8 may represent a novel route for the productive use of peroxide produced by Ero1 alpha during disulfide bond formation. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：503 / 515

页数：13

共 36 条

[1] ERp27, a new non-catalytic endoplasmic reticulum-located human protein disulfide isomerase family member, interacts with ERp57 [J].