PROBING BACTERIAL HOMOLOGUE OF GLUTAMATE TRANSPORTER BY PULSED DIPOLAR ESR

通过脉冲偶极 ESR 探测谷氨酸转运蛋白的细菌同源物

• 批准号: 8364071
• 负责人: ELKA R GEORGIEVA
• 金额: $ 5.56万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364071
• 关键词: Aspartate; Cell membrane; Cytosol; Funding; Glutamate Transporter; Glutamates; Goals; Grant; Homologous Gene; Membrane; Membrane Lipids; Molecular; Motion; National Center for Research Resources; Nature; Neuraxis; Neuroglia; Neurons; Neurotransmitters; Physiologic pulse; Physiological; Principal Investigator; Pyrococcus horikoshii; Research; Research Infrastructure; Resources; Sodium; Source; Structure; Technology; United States National Institutes of Health; cost; extracellular; insight; periplasm; symporter; uptake

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Glutamate is a major excitatory neurotransmitter in the central nervous system. Therefore, a considerable effort has been invested to understand the mechanisms controlling its extracellular and intracellular levels. Glutamate transporters, residing in the plasma membranes of glial cells and neurons, are primarily responsible for the transmitter uptake. The key insight into the functional mechanism of glutamate transporters has emerged from the crystal structures of an archaeal homologue, vis. sodium-aspartate symporter, from Pyrococcus horikoshii (GltPh), which provided the views of its periplasm- and cytosol-facing states [1-3]. The question, however, persists: how relevant are these structures to the structures of the transporter in the context of lipid membranes? Our goal is to demonstrate that the molecular motions observed crystallographically take place under physiological conditions in membrane-embedded transporter by means of EPR. 1. Yernool, D., Boudker, O., Jin, Y. & Gouaux, E. Nature 431, 811-8 (2004); 2. Boudker, O., Ryan, R. M., Yernool, D., Shimamoto, K. & Gouaux, E. Nature 445, 387-93 (2007); 3. Reyes, N., Ginter, C. & Boudker, O. Nature 462, 880-5 (2009).

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 谷氨酸是中枢神经系统中主要的兴奋性神经递质。因此，人们投入了大量的精力来了解控制其细胞外和细胞内水平的机制。谷氨酸转运蛋白存在于神经胶质细胞和神经元的质膜中，主要负责递质的摄取。对谷氨酸转运蛋白功能机制的关键见解是从古菌同系物的晶体结构中得出的。天冬氨酸钠同向转运蛋白，来自 Pyrococcus horikoshii (GltPh)，提供了其面向周质和细胞质状态的视图 [1-3]。 然而，问题仍然存在：这些结构与脂质膜中转运蛋白的结构有何相关性？我们的目标是证明通过 EPR 的方式在膜嵌入转运蛋白的生理条件下发生晶体学观察到的分子运动。 1. Yernool, D.、Boudker, O.、Jin, Y. 和 Gouaux, E. Nature 431, 811-8 (2004)； 2.布德克， O.、Ryan、R.M.、Yernool、D.、Shimamoto、K. 和 Gouaux，E. Nature 445， 387-93（2007）； 3. Reyes, N.、Ginter, C. 和 Boudker, O. Nature 462, 880-5 (2009)。