STRUCTURAL STUDIES OF GABA RECEPTORS

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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. Metabotropic GABA(B) receptors mediate inhibitory neurotransmission in the mammalian brain and are central to its function. GABA(B) receptors are G-protein coupled receptors (GPCRs) that regulate the activity of Ca2+ and K+ channels, and inhibit the function of adenylyl cyclase. Malfunction of GABA(B) receptors has been implicated in the development of a number of neurological diseases including spasticity, epilepsy and pain. Therefore, elucidating the structures of GABA(B) receptors would assist the design of valuable therapeutic agents. Our experiments are aimed at solving the ectodomain structures of GABA(B) receptors in the presence of various agonists and antagonists, and determining the characteristics of receptor-ligand interactions. We use x-ray diffraction data collected from protein crystals for structure determination. In addition to native data collection, multiple wavelength anomalous diffraction experiments at the selenium absorption edge will be carried out to obtain phases.