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).

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 谷氨酸是中枢神经系统中主要的兴奋性神经递质。因此，已经投入了大量努力来了解控制其细胞外和细胞内水平的机制。谷氨酸转运蛋白位于神经胶质细胞和神经元的质膜中，主要负责发射机的摄取。对谷氨酸转运蛋白的功能机理的关键见解是从古细菌同源物的晶体结构中出现的。来自horikoshii（GLTPH）的天冬氨酸钠s仪，它提供了其面向周期和细胞质的状态的视图[1-3]。 但是，问题仍然存在：在脂质膜的背景下，这些结构与转运蛋白的结构有多相关？我们的目标是证明通过EPR在膜上包含的转运蛋白的生理条件下观察到的分子运动在晶体学上发生。 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）。