Structure and Function of Metabolic Filaments

代谢丝的结构和功能

• 批准号: 10576292
• 负责人: Justin M Kollman
• 金额: $ 36.78万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10576292
• 关键词: 6-Phosphofructokinase; Allosteric Regulation; Biochemical; Biological; Biological Assay; Biological Models; Biophysics; Carbohydrates; Catabolic Process; Cells; Coupled; Critical Pathways; Cryoelectron Microscopy; DNA; Defect; Disease; Environment; Enzymes; Equilibrium; Failure; Filament; Funding; Glycolysis; Grant; Growth; Homeostasis; Human; In Vitro; Individual; Kinetics; Lateral; Life; Ligands; Liver; Mediating; Medical; Metabolic; Metabolic Control; Metabolism; Molecular; Mutation; Neuropathy; Nucleotide Biosynthesis; Nucleotides; Nutrient; Pathway interactions; Physiological; Play; Polymers; Process; Protein Isoforms; Pyrimidine; RNA; Reaction; Regulation; Ribonucleotides; Ribose; Role; Saccharomycetales; Side; Speed; Stress; Structure; Tissues; Work; Yeasts; design; enzyme activity; experimental study; glucose metabolism; in vivo; insight; polymerization; response; self assembly; single molecule; success; sugar

PROJECT SUMMARY Intermediate metabolism must be finely tuned, carefully balanced, and robustly adaptable to changes in environmental conditions. While the individual enzymes that drive most metabolic processes are well understood, only recently has the field come to appreciate the widespread role of metabolic enzyme self- assembly in metabolic organization and control. In particular, we now know that dozens of metabolic enzymes assemble into filamentous structures in vivo and in vitro, and that these filaments act as allosteric effectors to tune enzyme activity. This proposal focuses on self-assembled filaments of metabolic enzymes in glycolysis and nucleotide biosynthesis, processes that extract energy from sugar and generate fundamentally important macromolecular building blocks, respectively. We will use cryo-electron microscopy to determine the structural basis for assembly and regulation, coupled with biochemical, biophysical, and cell biological approaches in an integrative approach to understanding metabolic filament function. This work will provide insight into the specific roles polymerization plays in modulating enzyme function, and illuminate general principles of metabolic control by enzyme filaments.

项目总结