GPCR signaling complexes in living cells
活细胞中的 GPCR 信号复合物
基本信息
- 批准号:8718138
- 负责人:
- 金额:$ 24.75万
- 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:2007-09-25 至 2017-12-31
- 项目状态:已结题
- 来源:
- 关键词:AffinityAnabolismBinding SitesBiologicalBiological AssayBioluminescenceCell Surface ReceptorsCellsComplexDimerizationDrug PrescriptionsDrug TargetingEnergy TransferEquilibriumFamilyFluorescence Resonance Energy TransferG Protein-Coupled Receptor SignalingG-Protein-Coupled ReceptorsGoalsHybridsIndividualIntegral Membrane ProteinLeadLifeLigand BindingLigandsMembraneMembrane ProteinsMethodsModelingPharmaceutical PreparationsPropertyProteinsProtomerRhodopsinSamplingSignal TransductionSpecificityStructureTestingTimeTransfectionbasebiophysical techniquesdimerdrug of abuseinterestmembermonomernew therapeutic targetnovelprospectivepublic health relevancereceptorreceptor functionresearch studytherapeutic targettrafficking
项目摘要
DESCRIPTION (provided by applicant): G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors, and are the targets of a substantial fraction of all prescribed ad abused drugs. It is widely accepted that members of the largest GPCR family (class A receptors) self-assemble as dimers or higher-order oligomers, and GPCR dimers have been proposed as potential targets for novel therapeutic drugs. However, functional consequences of dimerization have been described for only a few receptors, and ligands that bind specifically to dimers have not been found. The main goal of this project is to test the hypothesis that most interactions between classes A protomers are both transient and structurally nonspecific. If this is the case, it would explain why dimerization is rarely leads to overt functional changes or unique binding sites. The objective of the proposed project is to determine the physical stability of interactions between a large sample of class A receptors and transmembrane control proteins using fluorescence resonance energy transfer (FRET), bioluminescence resonance energy transfer (BRET), time-resolved fluorescence resonance energy transfer (TR-FRET), and an affinity-based on-cell corecruitment assay. Inclusion of a large sample of non-GPCR control proteins will allow us to determine if physical interactions between classes A protomers are special, or are typical of interactions between polytopic transmembrane proteins in general. These experiments will better define the quaternary structure of the largest subfamily of GPCRs, and may force a revision of the standard model that currently motivates the search for dimer-selective drugs.
描述(由申请人提供):G蛋白偶联受体(GPCR)是细胞表面受体的最大家族,并且是所有处方和滥用药物的主要靶点。人们普遍认为,最大的GPCR家族(A类受体)的成员自组装为二聚体或更高阶的寡聚体,并且GPCR二聚体已被提议作为新型治疗药物的潜在靶标。然而,二聚化的功能后果已被描述为只有少数受体,和配体,结合特异性二聚体还没有被found. The主要目标,这个项目是为了测试的假设,大多数A类protomers之间的相互作用都是短暂的,结构上非特异性的。如果是这样的话,这将解释为什么二聚化很少导致明显的功能变化或独特的结合位点。该项目的目的是确定大样本的A类受体和跨膜控制蛋白之间的相互作用的物理稳定性,使用荧光共振能量转移(FRET),生物发光共振能量转移(BRET),时间分辨荧光共振能量转移(TR-FRET),和基于亲和力的细胞共募集试验。包含大量非GPCR对照蛋白的样品将使我们能够确定A类原聚体之间的物理相互作用是否是特殊的,或者通常是多位跨膜蛋白之间的典型相互作用。这些实验将更好地定义最大的GPCR亚家族的四级结构,并可能迫使修订目前激励寻找二聚体选择性药物的标准模型。
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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Nevin Alan Lambert其他文献
Nevin Alan Lambert的其他文献
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{{ truncateString('Nevin Alan Lambert', 18)}}的其他基金
Conventional and unconventional GPCR-G protein coupling
常规和非常规 GPCR-G 蛋白偶联
- 批准号:
10605361 - 财政年份:2022
- 资助金额:
$ 24.75万 - 项目类别:
Conventional and unconventional GPCR-G protein coupling
常规和非常规 GPCR-G 蛋白偶联
- 批准号:
10405394 - 财政年份:2022
- 资助金额:
$ 24.75万 - 项目类别:
Direct assessment of GPCR-transducer coupling and G protein subtype bias
GPCR-转导器耦合和 G 蛋白亚型偏差的直接评估
- 批准号:
10239055 - 财政年份:2018
- 资助金额:
$ 24.75万 - 项目类别:
Hydrophobic mismatch and self-association of TM proteins and beta2 adrenoreceptor
TM蛋白和β2肾上腺素受体的疏水错配和自缔合
- 批准号:
8208051 - 财政年份:2011
- 资助金额:
$ 24.75万 - 项目类别:
Hydrophobic mismatch and self-association of TM proteins and beta2 adrenoreceptor
TM蛋白和β2肾上腺素受体的疏水错配和自缔合
- 批准号:
8066178 - 财政年份:2011
- 资助金额:
$ 24.75万 - 项目类别:
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