Structure/function analysis of understudied pH-sensitive Kir4.2 channels in vitro with conformation specific nanobodies
使用构象特异性纳米体对正在研究的 pH 敏感 Kir4.2 通道进行体外结构/功能分析
基本信息
- 批准号:10217510
- 负责人:
- 金额:$ 15.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-15 至 2022-08-14
- 项目状态:已结题
- 来源:
- 关键词:ArrhythmiaAtrial Heart Septal DefectsBiochemicalBiochemistryBiological AssayC-terminalCellsCholesterolComplexCongenital diaphragmatic herniaCryoelectron MicroscopyDefectDependenceDetergentsDevelopmentDiabetes MellitusDiseaseDockingDown SyndromeDrug ScreeningDrug or chemical Tissue DistributionElectrophysiology (science)EpilepsyEpitopesFamilyFunctional disorderGenerationsGenesGoalsHomeostasisHomoHumanImmunoglobulin GIn VitroIndividualInflammationIon ChannelLeadLibrariesLipidsLiposomesMembrane LipidsMembrane PotentialsMembrane ProteinsMethodsMolecularMolecular ConformationMutationNon-Insulin-Dependent Diabetes MellitusPathologicPatientsPharmaceutical PreparationsPhosphatidylinositol 4,5-DiphosphatePhysiologicalPolyunsaturated Fatty AcidsPositioning AttributePotassiumPropertyProtein ChemistryProteinsProtocols documentationProximal Renal Tubular AcidosisPublishingRegulationResolutionRestStructureSurfaceSystemTestingTherapeuticTimeTissuesTracerVascular DiseasesWorkX-Ray Crystallographybaseextracellulargene producthuman diseaseimprovedin silicoin vitro testinginsightinward rectifier potassium channellarge scale productionmutantnanobodiesnovelnovel strategiesnovel therapeuticsparticleprogramsprotein purificationreconstitutionscreeningsimulationsmall moleculestable cell linesystemic juvenile idiopathic arthritistherapeutic targettoolweb site
项目摘要
Project Summary
Inward rectifying potassium (Kir) channels regulate excitability in many tissues, and
multiple diseases result from mutations of Kir channel genes. The long-term goal of
this project is to understand the molecular details of understudied pH-sensitive Kir4
sub-family channels. Previously, I defined molecular mechanisms of bulk anionic
lipid regulation of Kir2 channels. These previous studies were made possible by my
establishing a new expression system and purification protocols for eukaryotic Kir2
channels, as well as uniquely combining the multiple methods of (1) computational
docking simulations, (2) functional assays of purified proteins reconstituted in
synthetic liposomes, and (3) high resolution structure determination. These studies
provide a template for gaining new understanding of understudied pH-sensitive Kir4
channels at the molecular level. We will establish an efficient expression system
and a purification protocol for large scale purifications of Kir4.2 homo- and
Kir4.2/Kir5.1 hetero-tetramer proteins that are understudied as well as develop
nanobodies specific to functional states that will not only facilitate structure
determinations in certain functional states but also have therapeutic potentials.
Once established, we will utilize the same `triple combination' of approaches to
determine molecular details of these understudied channel regulation and function.
项目总结
项目成果
期刊论文数量(0)
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Sun Joo Lee其他文献
Sun Joo Lee的其他文献
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