STRUCTURAL STUDIES ON NEURORECEPTORS

神经感受器的结构研究

• 批准号: 8363338
• 负责人: Hiroyasu Furukawa
• 金额: $ 1.09万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363338
• 关键词: Alzheimer' s Disease; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Binding; Biochemical; Biological; Cations; Cleaved cell; Crystallography; Electrophysiology (science); Enzymes; Funding; Glutamates; Glycine; Goals; Grant; Integral Membrane Protein; Ion Channel; LDL-Receptor Related Proteins; Ligands; Light; Lipoprotein Receptor; Mediating; Membrane; Molecular; N-Methyl-D-Aspartate Receptors; National Center for Research Resources; Neurons; Peptide Hydrolases; Play; Principal Investigator; Production; Property; Proteins; Proteolysis; Research; Research Infrastructure; Resources; Sensory Receptors; Site-Directed Mutagenesis; Source; Structure; Synaptic Transmission; Synchrotrons; Techniques; United States National Institutes of Health; base; cost; gamma secretase; neurotransmission; physical property; receptor; three dimensional structure

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. The research in my group is aimed at understanding molecular basis for biological activity and physical properties of integral membrane receptors, enzymes and ion channels involved in neurotransmission. To achieve our goals, three-dimensional structures are determined primarily by x-ray crystallography and functional properties of target proteins are assessed by structure-based site-directed mutagenesis in combination with biophysical and biochemical techniques including electrophysiology. Specifically, we are focusing on three classes of integral membrane proteins, which play key roles in mediating neuronal activities: NMDA receptors, a ligand-gated cation channel that opens upon binding to glutamate and glycine and mediate excitatory synaptic transmission; LDL receptor related protein (LRP), a lipoprotein receptor that associate with NMDA receptors and regulate the strength of synaptic transmission; and gamma-secretase, an intramembrane cleaving protease (iCLIPs) that mediate regulated intramembrane proteolysis (RIP) of amyloid precursor protein (APP) to regulate the production of amyloid beta, a pathogenic product for Alzheimer's disease.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 我小组中的研究旨在了解积分膜受体，酶和与神经传递有关的离子通道的生物学活性和物理特性的分子基础。为了实现我们的目标，三维结构主要由X射线晶体学确定，目标蛋白的功能特性通过基于结构的位置定向诱变以及包括电生理学在内的生物物理和生化技术的结合来评估。 具体而言，我们专注于三类的整体膜蛋白，它们在介导神经元活性中起关键作用：NMDA受体，NMDA受体，这是一种配体门控阳离子通道，在与谷氨酸和甘氨酸结合并介导兴奋性突触传播后打开； LDL受体相关蛋白（LRP），一种与NMDA受体相关并调节突触传播强度的脂蛋白受体；和γ-分泌酶是一种膜内切割蛋白酶（ICLIP），可介导淀粉样蛋白前体蛋白（APP）调节的膜内蛋白水解（RIP），以调节淀粉样β的产生，淀粉样蛋白是阿尔茨海默氏病的致病产物。