SDSL-EPR STUDY OF INTERMEDIATE FILAMENT STRUCTURE
中间丝结构的 SDSL-EPR 研究
基本信息
- 批准号:7207948
- 负责人:
- 金额:$ 29.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-04-01 至 2011-02-28
- 项目状态:已结题
- 来源:
- 关键词:AccountingAffectAmino AcidsArchitectureAreaCellsCellular StructuresClassCoiled-Coil DomainConditionCrystallographyCytokeratinCytoplasmDataDesminDialysis procedureElectron Spin Resonance SpectroscopyEventExhibitsFigs - dietaryFilamentGenesHeadHumanIn VitroIntermediate FilamentsInterruptionK-18 conjugateKnowledgeLabelLeftLinkLocationMapsMembrane ProteinsModelingMonitorMutationOutputPathologicPatternPhenotypePhysical DialysisPhysiologic pulsePhysiologicalPoint MutationPositioning AttributeProcessPropertyProteinsPulse takingRandomizedRegistriesRelative (related person)ReporterResearch DesignSeveritiesSiteSolutionsSpin LabelsStagingStructureStutteringSurfaceTailTechniquesTestingTimeTranslatingUreaVimentinbasecrosslinkdimerdisease-causing mutationhuman diseasemonomermutantprotein aggregateprotein structureresearch studyretinal rodssizeultra high resolution
项目摘要
DESCRIPTION (provided by applicant): Intermediate filaments (IPs) are present in essentially every human cell. However, the inability to achieve crystal structure for intact IF proteins or IFs means that our understanding of IF structure is based in large part on predictions made from primary sequence and from limited cross-linking studies. Thus, most features of commonly presented models of IF structure are experimentally untested, or based on data which is open to alternative interpretation. This places serious limits on our ability to understand normal IF function, and the changes in IF assembly and structure that are caused by the many disease-causing mutations that have been identified in human IF genes.
We have demonstrated that site directed spin labeling and electron paramagnetic resonance can provide excellent structural information from intact IFs in physiologic conditions. We propose here to conduct an exhaustive study of the Type III IF protein vimentin, assembling the first comprehensive map of an intact intermediate filament. We will then conduct similar experiments on another Type III IF protein, desmin, and on cytokeratin IFs made from K8 and K18 to determine the degree to which IF assembly and structure are conserved among the three most common forms of intermediate filaments.
These studies will map the location and boundaries of alpha-helical, coiled-coil domains, linker regions, the conserved "stutter" found in all IF proteins, the boundaries of the rod domain, the surfaces of apposition between monomers in dimers, and between dinners in intact filaments, the registry and orientation of these dimers, and the sites of IF proteins that are available at the surface of the IF for interactions with other cellular proteins/structures. Sites within the head and tail domains that interact with one another, and with the rod domain will be mapped as well. Finally, we will explore the impact of known disease-causing mutations on IF assembly and structure.
描述(由申请人提供):中间丝(IP)基本上存在于每个人细胞中。然而,无法获得完整的IF蛋白或IF的晶体结构意味着我们对IF结构的理解在很大程度上是基于从一级序列和有限的交联研究中做出的预测。因此,大多数功能的IF结构的常见模型是未经实验测试,或基于数据是开放的替代解释。这严重限制了我们理解正常IF功能的能力,以及由人类IF基因中已鉴定的许多致病突变引起的IF组装和结构变化。
我们已经证明,在生理条件下,定向自旋标记和电子顺磁共振可以提供良好的结构信息,从完整的IF。我们建议在这里进行详尽的研究III型IF蛋白波形蛋白,组装完整的中间丝的第一个全面的地图。然后,我们将进行类似的实验上的另一种III型IF蛋白,结蛋白,并从K8和K18的细胞角蛋白IF,以确定在何种程度上IF组装和结构是保守的三种最常见的形式的中间丝。
这些研究将绘制α-螺旋、卷曲螺旋结构域、接头区域的位置和边界,在所有IF蛋白中发现的保守“口吃”,杆结构域的边界,二聚体中单体之间的并置表面,以及完整细丝中晚餐之间的并置表面,这些二聚体的注册和取向,以及在IF表面可用于与其它细胞蛋白/结构相互作用的IF蛋白的位点。头部和尾部结构域内彼此相互作用以及与杆结构域相互作用的位点也将被映射。最后,我们将探讨已知的致病突变对IF组装和结构的影响。
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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PAUL Gillespie FITZGERALD其他文献
PAUL Gillespie FITZGERALD的其他文献
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{{ truncateString('PAUL Gillespie FITZGERALD', 18)}}的其他基金
Regulation of Lens Fiber Cell Structure and Function by Post Translational Modification of Intermediate Filaments
通过中间丝的翻译后修饰调节晶状体纤维细胞结构和功能
- 批准号:
9217353 - 财政年份:2017
- 资助金额:
$ 29.49万 - 项目类别:
Regulation of Lens Fiber Cell Structure and Function by Post Translational Modification of Intermediate Filaments
通过中间丝的翻译后修饰调节晶状体纤维细胞结构和功能
- 批准号:
9900012 - 财政年份:2017
- 资助金额:
$ 29.49万 - 项目类别:
Non Fiber Cell Functions for the Beaded Filament Proteins
珠状丝蛋白的非纤维细胞功能
- 批准号:
8747592 - 财政年份:2014
- 资助金额:
$ 29.49万 - 项目类别:
SDSL-EPR STUDY OF INTERMEDIATE FILAMENT STRUCTURE
中间丝结构的 SDSL-EPR 研究
- 批准号:
7582267 - 财政年份:2006
- 资助金额:
$ 29.49万 - 项目类别:
SDSL-EPR STUDY OF INTERMEDIATE FILAMENT STRUCTURE
中间丝结构的 SDSL-EPR 研究
- 批准号:
7386600 - 财政年份:2006
- 资助金额:
$ 29.49万 - 项目类别:
SDSL-EPR Study of Intermediate Filament Structure
中间丝结构的SDSL-EPR研究
- 批准号:
8236802 - 财政年份:2006
- 资助金额:
$ 29.49万 - 项目类别:
SDSL-EPR STUDY OF INTERMEDIATE FILAMENT STRUCTURE
中间丝结构的 SDSL-EPR 研究
- 批准号:
7769871 - 财政年份:2006
- 资助金额:
$ 29.49万 - 项目类别:
SDSL-EPR Study of Intermediate Filament Structure
中间丝结构的SDSL-EPR研究
- 批准号:
8394915 - 财政年份:2006
- 资助金额:
$ 29.49万 - 项目类别:
SDSL-EPR Study of Intermediate Filament Structure
中间丝结构的SDSL-EPR研究
- 批准号:
8597426 - 财政年份:2006
- 资助金额:
$ 29.49万 - 项目类别:
SDSL-EPR STUDY OF INTERMEDIATE FILAMENT STRUCTURE
中间丝结构的 SDSL-EPR 研究
- 批准号:
7090181 - 财政年份:2006
- 资助金额:
$ 29.49万 - 项目类别:
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