PROBING BACTERIAL HOMOLOGUE OF GLUTAMATE TRANSPORTER BY PULSED DIPOLAR ESR

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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其胞外和胞内水平的控制机制。谷氨酸转运体存在于神经胶质细胞和神经元的质膜上，主要负责递质的摄取。对谷氨酸转运体作用机制的关键洞察来自于一种古老的同系物VIS的晶体结构。Horikoshii(GltPh)的钠-天冬氨酸转运体，它提供了其面向周质和细胞质的状态的观点[1-3]。然而，问题仍然存在：在脂膜的背景下，这些结构与转运蛋白的结构有多大的相关性？我们的目标是通过EPR证明在生理条件下观察到的分子运动发生在膜包埋转运体中。 1.Yernool，D.，Boudker，O.，jin，Y.&Gouaux，E.Nature 431,811-8(2004)；2.Boudker， 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容 387-93(2007)；3.雷耶斯，N.，金特，C.&Boudker，O.自然，462,880-5(2009)。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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).