PROBING BACTERIAL HOMOLOGUE OF GLUTAMATE TRANSPORTER BY PULSED DIPOLAR ESR

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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).