ERO1 蛋白和蛋白二硫键异构酶通路的体外功能分析。
Functional in vitro analysis of the ERO1 protein and protein-disulfide isomerase pathway.
机构信息
Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
出版信息
J Biol Chem. 2011 Sep 16;286(37):32705-12. doi: 10.1074/jbc.M111.227181. Epub 2011 Jul 8.
Abstract
Oxidative protein folding in the endoplasmic reticulum is supported by efficient electron relays driven by enzymatic reactions centering on the ERO1-protein-disulfide isomerase (PDI) pathway. A controlled in vitro oxygen consumption assay was carried out to analyze the ERO1-PDI reaction. The results showed the pH-dependent oxidation of PDI by ERO1α. Among several possible disulfide bonds regulating ERO1α activity, Cys(94)-Cys(131) and Cys(99)-Cys(104) disulfide bonds are dominant regulators by excluding the involvement of the Cys(85)-Cys(391) disulfide in the regulation. The fine-tuned species specificity of the ERO1-PDI pathway was demonstrated by functional in vitro complementation assays using yeast and mammalian oxidoreductases. Finally, the results provide experimental evidence for the intramolecular electron transfer from the a domain to the a' domain within PDI during its oxidation by ERO1α.
摘要
内质网中氧化蛋白折叠由酶促反应驱动的有效的电子接力支持，这些酶促反应以 ERO1-蛋白二硫键异构酶 (PDI) 途径为中心。进行了受控的体外耗氧测定来分析 ERO1-PDI 反应。结果表明 ERO1α 依赖于 pH 的 PDI 氧化。在几个可能调节 ERO1α 活性的二硫键中，Cys(94)-Cys(131)和 Cys(99)-Cys(104)二硫键是主要的调节剂，排除了 Cys(85)-Cys(391)二硫键在调节中的作用。使用酵母和哺乳动物氧化还原酶进行功能体外互补测定，证明了 ERO1-PDI 途径的精细物种特异性。最后，结果为 ERO1α 氧化 PDI 过程中，PDI 内从 a 结构域到 a'结构域的分子内电子转移提供了实验证据。
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