GLUTAMATE TRANSPORTER HOMOLOGUE FROM PYROCCOCUS HORIKOSHII

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 谷氨酸转运蛋白是一种膜蛋白，在神经传递过程中负责谷氨酸从突触间隙中的清除。 谷氨酸转运蛋白将底物摄取与钠、钾和质子的膜梯度偶联。 除了双偶联离子通量，它们还表现出非偶联阴离子通量，这是门控的基板结合。 最近，我们已经确定了来自Pyroccocus horikoshii的谷氨酸转运蛋白同系物（GltPh）的晶体结构（Nature 431：811-18，2004; Nature 445：387-93，2007）。 因此，已经证明，这种蛋白质捕获其哺乳动物同源物的许多功能特征，包括阴离子渗透。 我们计划使用含有重原子的阴离子来尝试定位阴离子渗透途径/结合位点。 这项工作将揭示这些有趣的和生理上非常重要的蛋白质的机制，结合联合收割机的离子耦合转运蛋白和离子通道的功能。

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 transporters are integral membrane proteins responsible for clearance of glutamate from the synaptic cleft following rounds of neurotransmission. Glutamate transporters couple substrate uptake to membrane gradients of sodium, potassium and protons. In addition to thermodynamically coupled ion fluxes they also demonstrate an uncoupled anion flux, which is gated by substrate binding. Recently we have determined the crystal structure of a glutamate transporter homologue from Pyroccocus horikoshii (GltPh) (Nature 431: 811-18, 2004; Nature 445: 387-93, 2007). It has been consequently demonstrated that this protein captures many functional features of its mammalian homologues, including anion permeation. We are planning to use anions containing heavy atoms to attempt to locate anion permeation pathway/binding sites. This work will shed light on the mechanism of these intriguing and physiologically hugely important proteins, that combine features of ion coupled transporters and ion channels.