The FAD- and O2-dependent reaction cycle of Ero1-mediated oxidative protein folding in the endoplasmic reticulum

被引：360

作者：

Tu, BP ^{[1
]}

Weissman, JS ^{[1
]}

机构：

[1] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA

来源：

MOLECULAR CELL | 2002年 / 10卷 / 05期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/S1097-2765(02)00696-2

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：

The endoplasmic reticulum (ER) supports disulfide formation through an essential protein relay involving Ero1p and protein disulfide isomerase (PDI). We find that in addition to having a tightly associated flavin adenine dinucleotide (FAD) moiety, yeast Ero1p is highly responsive to small changes in physiological levels of free FAD. This sensitivity underlies the dependence of oxidative protein folding on cellular FAD levels. FAD is synthesized in the cytosol but can readily enter the ER lumen and promote Ero1p-catalyzed oxidation. Ero1p then uses molecular oxygen as its preferred terminal electron acceptor. Thus Ero1p directly couples disulfide formation to the consumption of molecular oxygen, but its activity is modulated by free lumenal FAD levels, potentially linking disulfide formation to a cell's nutritional or metabolic status.

引用

页码：983 / 994

页数：12

共 44 条

[31] IDENTIFICATION AND CHARACTERIZATION OF THE ESCHERICHIA-COLI GENE DSBB, WHOSE PRODUCT IS INVOLVED IN THE FORMATION OF DISULFIDE BONDS IN-VIVO [J].