Tu Benjamin P, Weissman Jonathan S
Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California-San Francisco, San Francisco, CA 94143, USA.
Mol Cell. 2002 Nov;10(5):983-94. doi: 10.1016/s1097-2765(02)00696-2.
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.
内质网（ER）通过涉及Ero1p和蛋白质二硫键异构酶（PDI）的必需蛋白质中继来支持二硫键的形成。我们发现，酵母Ero1p除了具有紧密结合的黄素腺嘌呤二核苷酸（FAD）部分外，还对游离FAD生理水平的微小变化高度敏感。这种敏感性是氧化蛋白质折叠对细胞FAD水平依赖性的基础。FAD在细胞质中合成，但可以很容易地进入内质网腔并促进Ero1p催化的氧化反应。然后Ero1p使用分子氧作为其首选的末端电子受体。因此，Ero1p直接将二硫键的形成与分子氧的消耗联系起来，但其活性受到内质网腔游离FAD水平的调节，这可能将二硫键的形成与细胞的营养或代谢状态联系起来。
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