MOLECULAR GENETICS OF THE CYTOCHROME BC1 COMPLEX

描述：生命系统的一个重要特征是它们能够 进行高效的能量转换。 生物能量转换（ET）是 细胞能量（ATP）生产所需的一系列途径， 这对于许多细胞功能至关重要，包括大分子 生物合成、溶质转运、信号转导、趋化性、趋光性、 和产热作用。 该项目的长期目标是定义 ET 途径的细胞色素 (cyt) 成分，并了解它们 结构、功能机制和生物发生（即组装和 监管）。 兼性光养细菌（例如红细菌属） 为真核细胞器提供了一个优秀的模型系统。 外星人 复合体在生物体中广泛存在，其功能不正常 导致人类毁灭性的神经肌肉和线粒体疾病，并且 植物作物产量低。 该项目将继续生化和 ET复合物的分子遗传学，重点关注结构、功能和 膜结合的多亚基细胞色素 c 复合物（即 泛氢醌：细胞色素c氧化还原酶，或bc1复合物，以及最近 发现了细胞色素CB氧化酶）。 具体目标包括隔离和 FeS 蛋白（bc1 的一个亚基）突变体的表征 复杂）并分析其回复体，以更好地理解其作用 亚基参与对苯二酚氧化；的纯化和表征 FeS蛋白和R. capsulatus的两个亚基bc1亚复合体；工程 结构更简单的 bc1 复合物与结构灵活性相关 以及氧化还原酶之间的功能相似性；隔离和 影响多亚基细胞色素生物发生的新突变体的表征 c 复合物及其血红素和铁硫假体的掺入 团体；生物发生突变体的遗传分析和测定 其基因产物的细胞位置。 这些研究将增加我们 了解 bc1 复合体的结构和功能机制， 并为膜结合的生物发生提供重要见解 多亚基细胞色素 c 复合物在细胞 ET 过程中发挥作用，是一个重要的 生物过程远未完全被理解，即使在 细菌。 在这个更简单的系统中获得的见解普遍适用 结构更复杂但功能相似 细胞器衍生的 ET 复合物，对于阐明 线粒体疾病和衰老的分子基础。

DESCRIPTION: A vital characteristic of living systems is their ability to perform efficient energy conversion. Biological energy transduction (ET) is the ensemble of pathways necessary for cellular energy (ATP) production, which is essential for many cellular functions, including macromolecular biosynthesis, solute transport, signal transduction, chemotaxis, phototaxis, and thermogenesis. The long term goal of this project is to define the cytochrome (cyt) components of the ET pathways, and to understand their structure, mechanism of function and biogenesis (i.e., assembly and regulation). Facultative phototrophic bacteria (e.g., Rhodobacter species) provide an excellent model system for eukaryotic organelles. The ET complexes are widespread among living organisms, and their improper function leads to devastating neuromuscular and mitochondrial diseases in humans, and low crop yields in plants. The project will continue biochemical and molecular genetics of ET complexes, focusing on the structure, function, and biogenesis of membrane-bound, multisubunit cyt c complexes (i.e., the ubihydroquinone:cyt c oxidoreductase, or the bc1 complex, and the recently discovered cyt cb oxidase). The specific aims include the isolation and characterization of mutants of the FeS protein ( a subunit of the bc1 complex) and analysis of their revertants to better understand the role this subunit plays in quinol oxidation; purification and characterization of the FeS protein and the two subunit bc1 subcomplex of R. capsulatus; engineering of structurally simpler bc1 complexes to correlate structural flexibility and functional similarities between oxidoreductases; isolation and characterization of new mutants affecting the biogenesis of multisubunit cyt c complexes and incorporation of their heme and iron-sulfur prosthetic groups; and genetic analyses of biogenesis mutants and determination of cellular locations of their gene products. These studies will increase our understanding of the structure and mechanism of function of the bc1 complex, and provide important insights into the biogenesis of membrane-bound multisubunit cyt c complexes that operate during cellular ET, an important biological process which is far from being completely understood, even in bacteria. Insights gained in this simpler system are generally applicable to the structurally more complex and yet functionally similar organelle-derived ET complexes, and are important for the elucidation of the molecular basis of mitochondrial diseases and aging.