Mechanismus der Thioloxidase Mia40

硫醇氧化酶Mia40的机制

• 批准号: 186885367
• 负责人: Professor Dr. Franz-Xaver Schmid
• 金额: --
• 依托单位: Laboratorium für Biochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/186885367?language=en
• 关键词: Mechanismus; der; Thioloxidase; Mia40

Recently, disulfide-bonded proteins were found in the inter-membrane space of mitochondria, and a disulfide relay system was discovered that mediates the oxidative folding of these proteins. The key components of this system, Mia40 and Erv1 are essential for viability of yeast. The basic principles of their function in vivo and in vitro are known, and crystal and NMR structures of Mia40 and several substrate proteins are available. It is our aim to elucidate the kinetic mechanism of Mia40/Erv1- mediated oxidative folding at the molecular level. We will examine how Mia40 catalyzes the individual steps of thiol-disulfide exchange reactions in the substrate proteins, how conformational folding and Mia40-mediated disulfide bond formation are coupled, how the kinetics of Mia40 are affected by its co-factors Erv1 and Hot13, and, in particular, how Mia40 differs in its enzymatic mechanism from the thioldisulfide exchange enzymes that catalyze oxidative folding in the endoplasmic reticulum and in the bacterial periplasm. We expect that these studies will be helpful not only to understand the molecular mechanism of this newly discovered folding system in the mitochondria, but that it also provides a good access to understanding the basic molecular mechanisms of catalyzed oxidative folding.

近年来，在线粒体的膜间隙中发现了二硫结合蛋白，并发现了介导这些蛋白氧化折叠的二硫传递系统。该系统的关键成分Mia40和Erv1对酵母的生存能力至关重要。它们在体内和体外功能的基本原理是已知的，并且Mia40和几种底物蛋白的晶体和核磁共振结构是可用的。我们的目的是在分子水平上阐明Mia40/Erv1介导氧化折叠的动力学机制。我们将研究Mia40如何催化底物蛋白中硫醇-二硫交换反应的各个步骤，构象折叠和Mia40介导的二硫键形成如何耦合，Mia40的动力学如何受到其辅助因子Erv1和Hot13的影响，特别是Mia40在酶促机制上与内质网和细菌周质中催化氧化折叠的硫醇-二硫交换酶有何不同。我们期望这些研究不仅有助于理解线粒体中新发现的折叠系统的分子机制，而且也为理解催化氧化折叠的基本分子机制提供了一个很好的途径。

项目成果

Mia40 targets cysteines in a hydrophobic environment to direct oxidative protein folding in the mitochondria

• DOI: 10.1038/ncomms4041
• 发表时间: 2014-01-01
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Koch, Johanna R.;Schmid, Franz X.
• 通讯作者: Schmid, Franz X.

Mia40 is optimized for function in mitochondrial oxidative protein folding and import.

Mia40 针对线粒体氧化蛋白折叠和导入功能进行了优化

• DOI: 10.1021/cb500408n
• 发表时间: 2014
• 期刊: ACS chemical biology
• 影响因子: 4
• 作者: J. R. Koch ;F. X. Schmid
• 通讯作者: F. X. Schmid