MOLECULAR GENETICS OF THE CYTOCHROME BC1 COMPLEX

细胞色素 BC1 复合物的分子遗传学

• 批准号: 6324467
• 负责人: M. FEVZI DALDAL
• 金额: $ 8.01万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-12-01 至 2001-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6324467
• 关键词: Rhodospirillales; bacterial genetics; bioenergetics; cytochrome c; cytochrome oxidase; enzyme complex; enzyme mechanism; gene mutation; nucleic acid sequence; protein biosynthesis; protein engineering; protein purification; protein structure function; site directed mutagenesis

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.

描述：生命系统的一个重要特征是它们能够 进行有效的能量转换。 生物能量转换（ET） 细胞能量（ATP）产生所必需的途径的集合， 它是许多细胞功能所必需的，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 细胞色素（cyt）成分的ET途径，并了解他们的 结构、功能机制和生物起源（即，组件和 法规）。 兼性光养细菌（例如，红细菌属） 为真核细胞器提供了一个极好的模型系统。 的ET 复合物在生物体中广泛存在，它们的不当功能 导致人类神经肌肉和线粒体疾病， 作物产量低。 该项目将继续生物化学和 ET复合物的分子遗传学，侧重于结构，功能， 膜结合的多亚基CytC复合物的生物发生（即，的 泛氢醌：细胞色素C氧化还原酶，或bc 1复合物，以及最近的 发现了Cyt CB氧化酶）。 具体目标包括隔离和 FeS蛋白（bc 1的亚基）突变体的表征 复杂）和分析其回复突变体，以更好地了解这一作用， 亚基在醌醇氧化中的作用; FeS蛋白与R.工程学 结构上更简单的bc 1复合物， 和氧化还原酶之间的功能相似性;分离和 影响多亚基细胞色素生物发生的新突变体的表征 c络合物及其血红素和铁-硫辅基的掺入 生物发生突变体的遗传分析和确定 基因产物的细胞定位。 这些研究将增加我们的 了解bc 1复合物的结构和功能机制， 并提供了重要的见解的生物起源膜结合 多亚基cyt c复合物在细胞ET过程中起作用，是一种重要的 生物学过程，这是远远没有完全理解，即使在 细菌 在这个较简单的系统中获得的见解普遍适用 到结构上更复杂但功能上相似的 细胞器衍生的ET复合物，是重要的阐明 线粒体疾病和衰老的分子基础。