STRUCTURAL STUDIES OF GABA RECEPTORS

GABA 受体的结构研究

• 批准号: 7955187
• 负责人: QING R FAN
• 金额: $ 0.22万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955187
• 关键词: Adenylate Cyclase; Agonist; Brain; Characteristics; Computer Retrieval of Information on Scientific Projects Database; Data; Data Collection; Development; Epilepsy; Funding; G-Protein-Coupled Receptors; GABA Receptor; GABA-B Receptor; Grant; Institution; Ligands; Mediating; Pain; Phase; Potassium Channel; Proteins; Research; Research Personnel; Resources; Selenium; Source; Structure; Therapeutic Agents; United States National Institutes of Health; absorption; design; nervous system disorder; neurotransmission; receptor; research study; structural biology

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 代谢型 GABA(B) 受体介导哺乳动物大脑中的抑制性神经传递，并且是其功能的核心。 GABA(B) 受体是 G 蛋白偶联受体 (GPCR)，可调节 Ca2+ 和 K+ 通道的活性，并抑制腺苷酸环化酶的功能。 GABA(B) 受体功能障碍与许多神经系统疾病的发生有关，包括痉挛、癫痫和疼痛。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各种激动剂和拮抗剂存在下 GABA(B) 受体的胞外结构，并确定受体-配体相互作用的特征。我们使用从蛋白质晶体收集的 X 射线衍射数据来确定结构。除了原始数据收集外，还将在硒吸收边进行多波长反常衍射实验以获得相位。