STRUCTURE OF A GLUTAMATE RECEPTOR BINDING DOMAIN
谷氨酸受体结合域的结构
基本信息
- 批准号:7955584
- 负责人:
- 金额:$ 1.84万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-07-01 至 2010-06-30
- 项目状态:已结题
- 来源:
- 关键词:AgonistAmyotrophic Lateral SclerosisBindingBinding SitesBrainCationsCell membraneComputer Retrieval of Information on Scientific Projects DatabaseDiseaseDrug Delivery SystemsElectron Spin Resonance SpectroscopyEpilepsyExtracellular DomainFundingGluR2 subunit AMPA receptorGlutamate ReceptorGlutamatesGrantInstitutionIon ChannelIonsIschemic Brain InjuryLengthLigand BindingLigand Binding DomainLobeMeasurementMeasuresMotionNMR SpectroscopyNeuronsNeurotransmitter ReceptorProteinsResearchResearch PersonnelResourcesSourceStructureUnited States National Institutes of HealthWorkX-Ray Crystallographyextracellularflexibilityprotein functionreceptor binding
项目摘要
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.
Glutamate receptors are the major excitatory neurotransmitter receptors in vertebrate brain and are involved in a variety of normal and pathological neuronal functions. These proteins function by binding glutamate in an extracellular domain and opening an intrinsic ion channel that allows cations to flow in and out of the neuron. Drugs targeted to glutamate receptors may have considerable potential for treating such diverse disorders as epilepsy, amyotrophic lateral sclerosis, and ischemic brain damage. We are studying two important glutamate receptors (GluR2 and GluR3), using X-ray crystallography and NMR and ESR spectroscopy to understand the structure and dynamics and to compare the results with the function of the protein measured using single channel recording (measurement of ion conductance across the cell membrane). The structural work is done on the extracellular ligand-binding domains of the proteins (GluR2 S1S2 and GluR3 S1S2), which are a soluble constructs derived from the full-length proteins. The proteins have a bilobed structure with the binding site for glutamate and derivatives at the interface between the two lobes. For GluR2, previous work has suggested that the degree to which the lobes close upon binding of ligand may relate to the function of the protein. Our initial work with NMR spectroscopy and our recent crystal structures, suggest that the relationship between structure and function may be more complicated, involving protein flexibility. Obtaining additional structures, under conditions that reveal the range of possible motions, is essential for understanding the functional consequences of agonist binding.
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。
谷氨酸受体是脊椎动物脑内主要的兴奋性神经递质受体,参与多种正常和病理性神经元功能。这些蛋白质通过在细胞外结构域中结合谷氨酸并打开允许阳离子流入和流出神经元的内在离子通道来发挥作用。以谷氨酸受体为靶点的药物在治疗癫痫、肌萎缩侧索硬化和缺血性脑损伤等多种疾病方面可能具有相当大的潜力。我们正在研究两种重要的谷氨酸受体(GluR 2和GluR 3),使用X射线晶体学和NMR和ESR光谱来了解结构和动力学,并将结果与使用单通道记录(测量跨细胞膜的离子电导)测量的蛋白质功能进行比较。结构工作是在蛋白质的胞外配体结合结构域(GluR 2 S1 S2和GluR 3 S1 S2)上进行的,其是源自全长蛋白质的可溶性构建体。蛋白质具有双叶结构,在两叶之间的界面处具有谷氨酸和衍生物的结合位点。对于GluR 2,以前的工作表明,在配体结合后,叶关闭的程度可能与蛋白质的功能有关。我们最初的工作与NMR光谱和我们最近的晶体结构,表明结构和功能之间的关系可能更加复杂,涉及蛋白质的灵活性。在揭示可能运动范围的条件下获得额外的结构对于理解激动剂结合的功能后果是至关重要的。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ROBERT E OSWALD其他文献
ROBERT E OSWALD的其他文献
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{{ truncateString('ROBERT E OSWALD', 18)}}的其他基金
Structure, Activation, and Modulation of AMPA/Glutamate Receptors
AMPA/谷氨酸受体的结构、激活和调节
- 批准号:
8894107 - 财政年份:2014
- 资助金额:
$ 1.84万 - 项目类别:
Structure, Activation, and Modulation of AMPA/Glutamate Receptors
AMPA/谷氨酸受体的结构、激活和调节
- 批准号:
8759208 - 财政年份:2014
- 资助金额:
$ 1.84万 - 项目类别:
Structure, Activation, and Modulation of AMPA/Glutamate Receptors
AMPA/谷氨酸受体的结构、激活和调节
- 批准号:
9093854 - 财政年份:2014
- 资助金额:
$ 1.84万 - 项目类别:
Structure, Activation, and Modulation of AMPA/Glutamate Receptors
AMPA/谷氨酸受体的结构、激活和调节
- 批准号:
9282475 - 财政年份:2014
- 资助金额:
$ 1.84万 - 项目类别:
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