Biophysical characterization of chemokine receptors

趋化因子受体的生物物理特征

• 批准号: 6529765
• 负责人: NAVID MADANI
• 金额: $ 4.62万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6529765
• 关键词: X ray crystallography; biophysics; cytokine receptors; electrophysiology; gene expression; glutamate transporter; postdoctoral investigator; protein protein interaction; protein purification; protein structure function

DESCRIPTION (as provided by Applicant): The main goal of this proposal is to answer several unresolved fundamental questions regarding the structure and function of glutamate transporters. A series of experiments have been proposed to characterize the oligomeric structure of the functional transporters and to elucidate the structural features involved in subunit assembly and substrate selectivity. Specific aim 1 will characterize the oligomeric structure of glutamate transporters and will utilize the differences between transporter subtypes to map domains necessary for subunit assembly. In addition, heteromultimerization of neuronal specific transporters will be examined. This is a critical experiment since it has been shown that EAAT3 and EAAT4 neuronal transporters are expressed together in the Purkinje cells of cerebellum. The mutagenesis and biochemical techniques described in this proposal will determine the amino acid residues necessary for substrate selectivity among transporters. In specific aim 3, bacterial glutamate transporter will be purified in order to obtain x-ray diffractable crystals. Elucidating the molecular mechanisms underlying glutamate transporter function is essential in understanding synaptic transmission.

描述（由申请人提供）： 该提案的主要目标是回答几个尚未解决的基本问题 有关谷氨酸转运蛋白的结构和功能的问题。一个 已提出一系列实验来表征寡聚体 功能转运蛋白的结构并阐明其结构 涉及亚基组装和底物选择性的特征。具体目标1 将表征谷氨酸转运蛋白的寡聚结构，并将 利用转运蛋白亚型之间的差异来映射必要的域 用于子单元组装。此外，神经元特异性的异多聚化 运输商将接受检查。这是一个关键的实验，因为 表明 EAAT3 和 EAAT4 神经元转运蛋白在 小脑的浦肯野细胞。诱变和生化技术 该提案中描述的将确定所需的氨基酸残基 转运蛋白之间的底物选择性。在具体目标 3 中，细菌 谷氨酸转运蛋白将被纯化以获得X射线衍射 晶体。阐明谷氨酸转运蛋白的分子机制 功能对于理解突触传递至关重要。