Struture snd Dynamic Determinants of Ion Channel Assembly by Adapter Proteins
接头蛋白离子通道组装的结构和动态决定因素
基本信息
- 批准号:7643361
- 负责人:
- 金额:$ 38.48万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-07-15 至 2010-06-30
- 项目状态:已结题
- 来源:
- 关键词:AffinityArchitectureBacterial InfectionsBindingBinding SitesBiochemicalBiological ProcessCarrier ProteinsCell Surface ProteinsCell Surface ReceptorsCell membraneCell surfaceChloride IonChronicCommunicationComplexCoupledCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorCytoplasmic TailCytoskeletonDiseaseElementsEpithelialExhibitsGoalsHereditary DiseaseImmune systemIn VitroIon ChannelIon TransportLaboratoriesLiquid substanceLungMacromolecular ComplexesMammalian CellMembraneMolecularMolecular AnalysisMolecular StructureMotionMucous body substanceNeutronsPhosphorylationProtein Kinase CProteinsRegulationResearchRoentgen RaysSignal TransductionSignaling ProteinSodium ChlorideSolutionsSpectrum AnalysisStructureSurface Plasmon ResonanceTestingTherapeuticThickTissuesTransducersWorkadapter proteinbasecell growthdesignezrinlight scatteringmacromolecular assemblymigrationmutantnovelnovel therapeuticsprototypestoichiometrystructural biology
项目摘要
DESCRIPTION (provided by applicant): Cystic fibrosis is a devastating, chronic, progressive, and frequently fatal genetic disease that is particularly manifest in the lungs. The major cause is an abnormality in ion transport across cell membranes by the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is the dominant chloride ion transporter in several epithelial tissues. Two adapter proteins-Na+/H+ exchanger regulator factor (NHERF) and ezrin-regulate the cell surface concentrations of CFTR, organize the macromolecular interactions of CFTR with a network of signaling proteins for efficient transduction, and ultimately control the strength of chloride ion transport. The goal of this research is to determine the molecular mechanisms by which adapter proteins work in coordination to regulate the macromolecular assembly of CFTR. The central hypothesis to be tested is that NHERF is a signal transducer whose specific intra-molecular interactions, which are modulated by ezrin, control the ability of NHERF to assemble CFTR. By studying the architecture, energetics, and dynamics of the formation of CFTR macromolecular complexes assembled by multivalent adapter proteins, this research will provide a quantitative analysis of the molecular mechanisms by which adapter proteins interact to assembly CFTR channels. A molecular understanding of the macromolecular interactions with CFTR is an essential element for developing a therapeutic strategy for the cure of cystic fibrosis.
描述(由申请人提供):囊性纤维化是一种破坏性的、慢性的、进行性的、经常致命的遗传性疾病,特别是在肺部。主要原因是囊性纤维化跨膜传导调节因子(CFTR)跨细胞膜的离子转运异常。CFTR是几种上皮组织中的主要氯离子转运蛋白。两个衔接蛋白-Na +/H+交换调节因子(NHERF)和ezrin-调节CFTR的细胞表面浓度,组织CFTR与信号蛋白网络的大分子相互作用以进行有效的转导,并最终控制氯离子转运的强度。本研究的目的是确定衔接蛋白协同调节CFTR大分子组装的分子机制。待检验的中心假设是NHERF是一种信号转导子,其特定的分子内相互作用(由埃兹蛋白调节)控制NHERF组装CFTR的能力。通过研究多价衔接蛋白组装的CFTR大分子复合物的结构、能量学和动力学,本研究将提供衔接蛋白相互作用组装CFTR通道的分子机制的定量分析。对大分子与CFTR相互作用的分子理解是开发治疗囊性纤维化的治疗策略的基本要素。
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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{{ truncateString('ZIMEI BU', 18)}}的其他基金
USING NMR TO MEASURE THE SELF-DIFFUSION OF EZRIN COMPLEXES
使用 NMR 测量 Ezrin 复合物的自扩散
- 批准号:
8169019 - 财政年份:2010
- 资助金额:
$ 38.48万 - 项目类别:
TRAINING IN THE USE OF BRUKER AND VARIAN SPECTROMETERS AND NMR
布鲁克和瓦里安光谱仪和核磁共振的使用培训
- 批准号:
8169020 - 财政年份:2010
- 资助金额:
$ 38.48万 - 项目类别:
Struture snd Dynamic Determinants of Ion Channel Assembly by Adapter Proteins
接头蛋白离子通道组装的结构和动态决定因素
- 批准号:
7841184 - 财政年份:2009
- 资助金额:
$ 38.48万 - 项目类别:
Struture snd Dynamic Determinants of Ion Channel Assembly by Adapter Proteins
接头蛋白离子通道组装的结构和动态决定因素
- 批准号:
7320051 - 财政年份:2007
- 资助金额:
$ 38.48万 - 项目类别:
Struture snd Dynamic Determinants of Ion Channel Assembly by Adapter Proteins
接头蛋白离子通道组装的结构和动态决定因素
- 批准号:
8101409 - 财政年份:2007
- 资助金额:
$ 38.48万 - 项目类别:
Struture snd Dynamic Determinants of Ion Channel Assembly by Adapter Proteins
接头蛋白离子通道组装的结构和动态决定因素
- 批准号:
7471373 - 财政年份:2007
- 资助金额:
$ 38.48万 - 项目类别:
Struture snd Dynamic Determinants of Ion Channel Assembly by Adapter Proteins
接头蛋白离子通道组装的结构和动态决定因素
- 批准号:
7880184 - 财政年份:2007
- 资助金额:
$ 38.48万 - 项目类别:
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