Cardiac Myosin Binding Protein-C: Structure, Function, and Regulation
心肌肌球蛋白结合蛋白-C:结构、功能和调节
基本信息
- 批准号:8215771
- 负责人:
- 金额:$ 205.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-02-01 至 2015-01-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAccountingActinsActivities of Daily LivingActomyosinAddressAdrenergic AgentsAffectAmericanAnimalsArrhythmiaArtsAttentionBehaviorBeliefBindingBiological AssayBiologyBiophysicsC2 DomainCardiacCardiac MyosinsCardiomyopathiesCardiovascular DiseasesCardiovascular systemCause of DeathCessation of lifeCharacteristicsClinicalCollaborationsConsensusContractile ProteinsCytoskeletal ProteinsDataDefectDiagnosisDilated CardiomyopathyDiseaseElectron MicroscopyElectronsEtiologyEventFamilial Hypertrophic CardiomyopathyFiberFilamentFoundationsFutureGene MutationGenerationsGeneticGoalsGrantHeadHead and neck structureHealthHealth Care CostsHeartHeart DiseasesHeart HypertrophyHeart failureHumanHypertrophic CardiomyopathyHypertrophyIn VitroIndividualInheritedInstitutionInvestigationLaboratoriesLasersLeadLeftLinkLocationMassachusettsMeasurementMechanicsMedicineMicrofilamentsMicroscopicMissionModelingMolecularMolecular BiologyMolecular MotorsMolecular StructureMotorMusMuscleMuscle CellsMuscle FibersMutagenesisMutant Strains MiceMutationMyocardiumMyofibrilsMyosin ATPaseMyosin Heavy ChainsNational Heart, Lung, and Blood InstituteOrganOutcomePatientsPerformancePhosphorylationPhysiologicalPhysiologyPlayPoint MutationPopulationPost-Translational Protein ProcessingPreparationPreventionProductionProductivityProtein BindingProteinsPumpRegulationResearchResearch PersonnelResolutionRoleSarcomeresScientistSite-Directed MutagenesisSkinStructural BiologistStructureStructure-Activity RelationshipSudden DeathTechniquesTherapeutic InterventionThickThick FilamentThin FilamentTimeTransgenic MiceUnited StatesUniversitiesVentricularVermontadrenergicbasecell motilitycitrate carrierclinical phenotypeconnectinheart cellimprovedinsightinterestmedical schoolsmolecular mechanicsmouse modelmultidisciplinarymutantmyosin-binding protein Cprematureprogramsreconstructionresearch facilitysingle moleculespatial relationshipstructural biologysudden cardiac deaththerapeutic target
项目摘要
Mutations in cardiac myosin binding protein-C (cMyBP-C) lead to sudden death in young individuals
with Familial Hypertrophic Cardiomyopathy. Despite Its clinical importance and its association with the
actomyosin molecular motor of the heart, a significant gap still remains in understanding how cMyBP-C
modulates cardiac power production. In addition, cMyBP-C is phosphorylated following p-adrenergic
stimulation, suggesting that cMyBP-C Itself may be regulated in a phosphorylation-dependent manner.
This Program Project (3 projects and 3 cores) will provide a comprehensive molecular understanding of
cMyBP-C function, its regulation by phosphorylation, and its impact on cardiac contractility. Using state-ofthe-
art techniques, we will characterize cMyBP-C's structure and function through studies ranging from the
mechanics of the whole heart down to interactions between a single cMyBP-C molecule and the
actomyosin molecular motor. Project #1 will use high resolution 3-dimensional electron microscopic
reconstruction to characterize the structure of cMyBP-C and its sarcomeric organization, providing insight
to its functional capacity. Project #2 will use the laser trap to assess cMyBP-C's ability to modulate
actomyosin power production at the single molecule level, while Project #3 will use transgenic mouse
models to define the role of cMyBP-C's putative actin-binding and its phosphorylation on cardiac function
under various physiological conditions. The Ventricular and Cardiac Fiber Characterization and Integration
Core (Core B) will gather the ventricular performance and fiber mechanical data to bridge the physiological
gap between the single molecule and whole animal studies. In addition, the Core will provide a modeling
platform to integrate the data from all physiological levels into a mechanistic model of cMyBP-C
functionality. The Mouse and cMyBP-C Protein Production Core (Core C) will generate mice with mutant
cMyBP-C and in vitro expression of mutant cMyBP-C protein at its actin-binding and phosphorylation
domains. These hearts and protein will be studied at all anatomical levels by the various projects. The
Program Project's long term goals are to: 1) define cMyBP-C's molecular structure and sarcomeric
organization; 2) determine how cMyBP-C modulates cardiac function in a phosphorylation-dependent
manner; 3) define why alterations in cMyBP-C phosphorylation are associated with heart failure in
humans.
心肌肌球蛋白结合蛋白c (cMyBP-C)突变可导致年轻人猝死
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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David M Warshaw其他文献
David M Warshaw的其他文献
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{{ truncateString('David M Warshaw', 18)}}的其他基金
Cargo Transport by Myosin Va and Kinesin-1 Molecular Motors: In Vitro Model Systems that Build Complexity in 3-Dimensions.
Myosin Va 和 Kinesin-1 分子马达的货物运输:构建 3 维复杂性的体外模型系统。
- 批准号:
10393000 - 财政年份:2021
- 资助金额:
$ 205.49万 - 项目类别:
Cargo Transport by Myosin Va and Kinesin-1 Molecular Motors: In Vitro Model Systems that Build Complexity in 3-Dimensions.
Myosin Va 和 Kinesin-1 分子马达的货物运输:构建 3 维复杂性的体外模型系统。
- 批准号:
10204620 - 财政年份:2021
- 资助金额:
$ 205.49万 - 项目类别:
Equipment supplement - Refeyn TwoMP iSCAT microscope
设备补充 - Refeyn TwoMP iSCAT 显微镜
- 批准号:
10784112 - 财政年份:2021
- 资助金额:
$ 205.49万 - 项目类别:
Cargo Transport by Myosin Va and Kinesin-1 Molecular Motors: In Vitro Model Systems that Build Complexity in 3-Dimensions.
Myosin Va 和 Kinesin-1 分子马达的货物运输:构建 3 维复杂性的体外模型系统。
- 批准号:
10605333 - 财政年份:2021
- 资助金额:
$ 205.49万 - 项目类别:
Cardiac Myosin-Binding Protein C: Molecular Modulation of Actomyosin Function.
心肌肌球蛋白结合蛋白 C:肌动球蛋白功能的分子调节。
- 批准号:
8860500 - 财政年份:2015
- 资助金额:
$ 205.49万 - 项目类别:
Cardiac Myosin-Binding Protein C: Molecular Modulation of Actomyosin Function.
心肌肌球蛋白结合蛋白 C:肌动球蛋白功能的分子调节。
- 批准号:
9128036 - 财政年份:2015
- 资助金额:
$ 205.49万 - 项目类别:
Cardiac Myosin-Binding Protein C: Molecular Modulation of Actomyosin Function.
心肌肌球蛋白结合蛋白 C:肌动球蛋白功能的分子调节。
- 批准号:
9282730 - 财政年份:2015
- 资助金额:
$ 205.49万 - 项目类别:
Myosin Va and VI Cargo Transport: In Vitro Model Systems
肌球蛋白 Va 和 VI 货物运输:体外模型系统
- 批准号:
8103714 - 财政年份:2011
- 资助金额:
$ 205.49万 - 项目类别:
Myosin Va and VI Cargo Transport: In Vitro Model Systems
肌球蛋白 Va 和 VI 货物运输:体外模型系统
- 批准号:
8248783 - 财政年份:2011
- 资助金额:
$ 205.49万 - 项目类别:
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