Structural Studies of Sugar Transporters

糖转运蛋白的结构研究

• 批准号: 8035627
• 负责人: DANENG WANG
• 金额: $ 9.97万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8035627
• 关键词: Affinity; Amino Acids; Arginine; Binding; Binding Sites; Biochemical; Biochemistry; Biological Assay; C-terminal; Cells; Charge; Complex; Crystallization; Data; Electron Spin Resonance Spectroscopy; Escherichia coli; Family; Funding; Glucose Transporter; Glycogen Storage Disease; High temperature of physical object; Homologous Gene; Human; Inorganic Phosphate Transporter; Kinetics; Maps; Measures; Mediating; Membrane Transport Proteins; Methods; Molecular Conformation; Muscle; Mutagenesis; Mutate; Mutation; Non-Insulin-Dependent Diabetes Mellitus; Organophosphates; Pathogenesis; Phase; Play; Process; Research Personnel; Resolution; Role; Side; Site; Spin Labels; Structure; Substrate Specificity; Suspension substance; Suspensions; Techniques; Temperature; Testing; Transmembrane Transport; Vesicle; alpha-glycerophosphoric acid; conformer; glucose 6-phosphate(transporter); glucose uptake; improved; member; novel; programs; reconstitution; structural biology; sugar

Membrane transport, for example glucose uptake, Is essential to the cell. Such processes are often mediated by secondary membrane transporters. The largest secondary transporter family is the major facilitator superfamily (MFS), with more than 5,000 members identified to date, including the glucose transporter from muscle (Glut4) and the glucose-6-phosphate transporter (G6PT), both from human and both are involved in the pathogenesis of type 2 diabetes. We propose to study the transport mechanisms of a bacterial homolog of Glut4 and G6PT, the glycerol-3-phosphate transporter (GIpT) from E. coli, using structural biology, biochemistry and spectroscopic approaches. In the previous funding cycle, we determined the crystal structure of GIpT in a substrate-free form at 3.3 A resolution. The structure suggests a "rocker-switch" mechanism for substrate transport. In the next funding cycle, to better understand GIpT's substrate specificity and substrate-induced conformational change, we plan to determine the crystal structures of the transporter in two substrate-bound forms. We will also test the rocker-switch mechanism and examine the role that key amino acid residues play using mutagenesis, transport assays and spectroscopic techniques. The structural and mechanistic information gained from GIpT can be used directly to improve our understanding of Glut4 and G6PT.

膜运输，例如葡萄糖的摄取，是细胞所必需的。这些过程通常是经过调解的