Assembly of the membrane-bound FeS centre of the Na+-translocating NQR

Na 转位 NQR 膜结合 FeS 中心的组装

• 批准号: 311211092
• 负责人: Privatdozent Dr. Günter Fritz
• 金额: --
• 依托单位: Fachgebiet Molekulare Mikrobiologie (190 h)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/311211092?language=en
• 关键词: Assembly; membrane; bound; FeS; centre

Iron is an essential element of life and participates in many cellular reactions. In complex with sulfur, two or more Fe atoms can form iron-sulfur clusters which facilitate many different enzymatic reactions. In the respiratory chain, many enzymes rely on FeS centers to catalyse redox-driven proton or Na+ transport. Typically, the FeS centers are bound to the peripheral part of the respiratory enzyme, but the Na+ -translocating NADH:quinone oxidoreductase (NQR) harbors an unprecedented FeS cluster bound within the membrane part of the complex. The NQR is a respiratory Na+ pump found in many gram-negative bacteria, including pathogenic Vibrio cholerae. In this collaborative research project, the properties and the assembly of this novel, membrane-bound FeS cluster of NQR will be studied using microbiological, biochemical and biophysical techniques. Previous results suggested an unusual ligation of the cluster which will be studied by X-ray crystallographic structure determination of improved crystals of holo-NQR. In addition, we will address the pathway of insertion of the FeS cluster to NQR by studying the structure and function of the FeS carrier protein NqrM. Our goals are the complete reconstruction of the iron-sulfur delivery pathway to the novel FeS center in NQR, and an understanding of the catalytic role of this membrane-bound FeS center in redox-driven Na+ -transport by NQR.

铁是生命的基本元素，参与许多细胞反应。在与硫的络合物中，两个或多个铁原子可以形成铁硫簇，促进许多不同的酶促反应。在呼吸链中，许多酶依赖于FeS中心来催化氧化还原驱动的质子或Na+运输。通常，FeS中心结合到呼吸酶的外周部分，但是Na+ -易位的NADH：醌氧化还原酶（NQR）在复合物的膜部分内结合了前所未有的FeS簇。NQR是在许多革兰氏阴性细菌中发现的呼吸Na+泵，包括致病性霍乱弧菌。在这个合作研究项目中，将使用微生物，生物化学和生物物理技术研究这种新型的，膜结合的FeS簇NQR的性能和组装。以前的结果表明，一个不寻常的连接的集群，这将是通过X射线晶体结构测定的改进的晶体的全息NQR研究。此外，我们将通过研究FeS载体蛋白NqrM的结构和功能来解决FeS簇插入NQR的途径。我们的目标是完全重建的铁-硫传递途径的新FeS中心在NQR，并了解这个膜结合的FeS中心在氧化还原驱动的Na+ -运输NQR的催化作用。