Bacterial cytochrome bc1:structure, function, biogenesis

细菌细胞色素 bc1：结构、功能、生物发生

• 批准号: 7933140
• 负责人: M. FEVZI DALDAL
• 金额: $ 4.17万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7933140
• 关键词: Aging; Anabolism; Bacteria; Binding; Biochemical; Biogenesis; Biological; Biological Models; Catalysis; Cell physiology; Characteristics; Chemicals; Communication; Complex; Cytochrome bc1 Complex; Cytochromes; Cytochromes b; Development; Devices; Disease; Distant; Electrons; Elements; Enzymes; Equilibrium; Event; Family; Future; Genetic; Goals; Grant; Health; Heme; Homologous Gene; Integral Membrane Protein; Knowledge; Life; Light; Link; Location; Membrane; Mitochondria; Modeling; Molecular; Molecular Genetics; Monitor; Motion; Movement; Muscle; Organelles; Organism; Oxidation-Reduction; Pathway interactions; Physiological; Plants; Process; Production; Property; Prosthesis; Protein Subunits; Proteins; Proteomics; Qi; Reaction; Resolution; Rhodobacter; Sampling; Side; Signal Transduction; Site; Structure; Sum; System; Thermogenesis; Time; Variant; bacterial genetics; base; cytochrome c; follow-up; human disease; innovation; insight; member; membrane biogenesis; nervous system disorder; novel; prototype; three dimensional structure

DESCRIPTION (provided by applicant): A vital characteristic of living systems is their ability to produce biological energy (ATP) efficiently. ATP is essential for cellular functions including biosynthesis, transport, signal transduction, chemo- and photo-taxis and thermogenesis. Energy producing complexes are widespread among organisms, and their improper function leads to devastating health problems and human diseases and low crop yields in plants. The long-term goal of this project is to understand the structure, mechanism of function and biogenesis of cytochrome (cyt) components of energy pathways. Bacteria provide excellent model systems for these studies that are pertinent to eukaryotic organelles. This project will use molecular genetics, proteomics, biochemical and biophysical approaches, with a sharp focus on the critical links between the structure-function and the biogenesis of the membrane-bound cyt bc1. This is a crucial enzyme whose absence or malfunction is the cause of multiple human diseases, including many muscular and neurological disorders. Resolution of the 3D structure of the cyt bc1 revealed the mobility of its FeS protein subunit, and is now leading to a chemical description of its mechanism of function, while our understanding of its biogenesis remains rudimentary even in simpler bacteria. The specific aims include probing the control mechanisms of the FeS protein motion to avoid unwanted side reactions, creating novel bc1 complex variants to visualize the internal reaction steps that are difficult to monitor, and characterizing novel biogenesis components of energy transducing cyt c complexes, including incorporation of their prosthetic groups. These studies will greatly enhance our understanding and knowledge of the structure, mechanism of function and biogenesis of the cyt bc1 as a prototype enzyme. Insights gained using this simpler system are generally applicable to the structurally more complex and yet functionally similar organelle-derived complexes, and could provide guiding lights for elucidating the molecular bases of mitochondrial and other human diseases and aging.

描述（由申请人提供）：生命系统的一个重要特征是它们有效产生生物能（ATP）的能力。ATP对细胞功能至关重要，包括生物合成、运输、信号转导、趋化和光趋化以及产热。产生能量的复合物在生物体中广泛存在，它们的功能不当导致毁灭性的健康问题和人类疾病以及植物的低产量。本项目的长期目标是了解细胞色素（cyt）能量通路组分的结构、功能机制和生物发生。细菌为这些与真核细胞器相关的研究提供了极好的模型系统。本项目将运用分子遗传学、蛋白质组学、生物化学和生物物理学等方法，重点研究膜结合细胞bc1的结构、功能和生物发生之间的关键联系。这是一种至关重要的酶，它的缺失或功能障碍是多种人类疾病的原因，包括许多肌肉和神经疾病。对cyt bc1三维结构的解析揭示了其FeS蛋白亚基的可移动性，目前正在对其功能机制进行化学描述，而我们对其生物发生的了解即使在更简单的细菌中也仍处于初级阶段。具体目标包括探索FeS蛋白运动的控制机制，以避免不必要的副反应，创建新的bc1复合物变体，以可视化难以监测的内部反应步骤，以及表征能量转导cyt - c复合物的新型生物发生成分，包括其假基的结合。这些研究将极大地增进我们对作为原型酶的cyt bc1的结构、功能机制和生物发生的理解和认识。使用这种更简单的系统获得的见解通常适用于结构更复杂但功能相似的细胞器衍生复合物，并可以为阐明线粒体和其他人类疾病和衰老的分子基础提供指导。