BACTERIAL CYTOCHROME BC1: STRUCTURE, FUNCTION, BIOGENESIS

细菌细胞色素 BC1：结构、功能、生物发生

• 批准号: 8118695
• 负责人: M. FEVZI DALDAL
• 金额: $ 2.49万
• 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 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8118695
• 关键词: Address; Aerobic; Aging; Air; Amino Acids; Anabolism; Apoptosis; Architecture; Binding; Biochemical; Biogenesis; Biological; Biological Models; Catalysis; Cell physiology; Cells; Cessation of life; Characteristics; Communication; Complex; Cytochrome bc1 Complex; Cytochromes; Cytochromes b; Defect; Degenerative Disorder; Development; Diagnosis; Disease; Electron Transport Complex III; Enzymes; Event; Exhibits; Funding; Generations; Genetic; Goals; Grant; Health; Human; Hydroquinones; Inherited; Knowledge; Life; Ligand Binding; Ligands; Link; Lipids; Malignant Neoplasms; Maps; Membrane; Mitochondria; Mitochondrial Diseases; Modeling; Molecular; Molecular Genetics; Myopathy; Neuropathy; Organelles; Organism; Ornithine; Oxidoreductase; Oxygen; Pain; Pathway interactions; Physiologic Thermoregulation; Physiological; Plants; Process; Production; Prokaryotic Cells; Property; Protein Disulfide Isomerase; Proteins; Protons; Reaction; Reactive Oxygen Species; Regulation; Research; Rhodobacter; Role; Signal Transduction; Site; Source; Stimulus; Structure; System; Thermogenesis; Trust; Variant; Wakefulness; base; cytochrome c; dimer; disulfide bond; human disease; innovation; insight; interdisciplinary approach; microbial; monomer; mutant; nervous system disorder; neuromuscular; novel; oxidation; public health relevance; response; sleep regulation

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 as well as 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 transduction pathways. These are important enzymes whose absence, or malfunction are the causes of multiple human diseases, including many muscular and neurological disorders. For these studies, prokaryotes provide simpler model systems that are evolutionarily conserved and closely related to eukaryotic organelles. This project uses molecular genetics, biochemical and biophysical approaches, with a sharp focus on the structure and function of the cyt bc1 or Complex III. The specific aims of this proposal include 1- the molecular basis of oxygen tolerance of the quinol oxidation site of the cyt bc1 to address how this aerobic enzyme avoids the production of unwanted reactive oxygen species in the presence of oxygen, 2- exploration of the Zn binding residues of cyt b at the Qo site to probe their involvement in H+ conduction, and 3- development and characterization of heterodimer cyt bc1 variants to address intra- and inter-monomer structural and functional communications and regulations within the cyt bc1, to probe the links between the dimeric architecture and the mechanism of function of this enzyme. These studies are expected to greatly enhance our understanding and knowledge of energy transduction enzymes. Information gained using the simpler bacterial system could be generally applicable to the structurally more complex but functionally similar and evolutionarily related organelle-derived enzyme, and could provide invaluable information for elucidating the molecular bases and diagnoses of mitochondrial and other human diseases, including neuropathies, myopathies and aging. PUBLIC HEALTH RELEVANCE: This research aims to define the structure-function and biogenesis of energy transduction enzymes. These proteins are the major sources of reactive oxygen species that are extremely harmful for human cells, and their biogenesis components form the molecular bases of many common mitochondrial diseases in humans. Malfunction of these enzymes induce multiple human illnesses, extending from maternally inherited mitochondrial diseases to neuromuscular degenerative disorders, as well as cancer and aging.

描述（由申请人提供）：