STRUCTURAL STUDIES OF GABA RECEPTORS

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。 代谢型GABA（B）受体介导哺乳动物脑中的抑制性神经传递，并且是其功能的中心。GABA（B）受体是一种G蛋白偶联受体（GPCR），可调节Ca ~（2+）和K ~+通道的活性，抑制腺苷酸环化酶的功能。GABA（B）受体的功能障碍与包括痉挛、癫痫和疼痛在内的许多神经系统疾病的发展有关。因此，阐明GABA（B）受体的结构将有助于设计有价值的治疗药物。我们的实验旨在解决GABA（B）受体在各种激动剂和拮抗剂存在下的胞外域结构，并确定受体-配体相互作用的特征。我们使用从蛋白质晶体中收集的X射线衍射数据进行结构测定。除了原生数据收集之外，还将在硒吸收边进行多波长异常衍射实验以获得相位。

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.