Allosteric Role of Dynein Light Chains in Dynein Assembly and Regulation
动力蛋白轻链在动力蛋白组装和调节中的变构作用
基本信息
- 批准号:0818896
- 负责人:
- 金额:$ 78.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-08-01 至 2013-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Cytoplasmic dynein is a microtubule-based molecular motor that uses the energy derived from ATP hydrolysis to move and transport cellular cargo towards the minus ends of microtubules. This transport is essential in several aspects of cell behavior including cell migration and division, chromosome segregation, and vesicle trafficking. The dynein heavy chain subunits bind to microtubules and contain the ATP sites that provide the motive force, while the light and intermediate chains are thought to bind to cargo and regulate the activity of the motor. Recent data from the Barbar lab have suggested that the role of light chain LC8 is to facilitate dimerization of the natively disordered N-terminal domain of dynein intermediate chain, rather than to primarily function as a cargo adaptor, as commonly thought. Light chain Tctex-1, which is a structural homolog of LC8 and binds the intermediate chain at a site contiguous to the LC8 binding site, is likely to have a similar role as LC8. The research project will test the hypothesis that the tandem roles of light chains LC8 and Tctex-1 are to promote dynein assembly and the interaction with the cargo adaptor dynactin, and not to act as cargo adaptors themselves. Using a combination of biophysical approaches including nuclear magnetic resonance spectroscopy (NMR), isothermal titration calorimetry and X-ray crystallography, the Barbar lab will elucidate the mechanisms of three important outcomes of the interactions of both light chains to dynein intermediate chain: 1) how they contribute to formation of a tight dynein assembly, 2) how they promote dimerization of the intermediate chain, and 3) how they may promote a tighter interaction of the intermediate chain with p150Glued subunit of dynactin. The essential roles of these light chains will be tested in vivo in the lab of Professor Tom Hays, a collaborator on this project. The studies should provide novel insights into the structural biology and thermodynamics of dynein motor function, and will complement the cell biological approaches that predominate in the field of intracellular transport. Since these studies provide the first structural insights into the role of the disorder-to-order transition in dynein assembly and its association with dynactin, they allow the opportunity to develop a tractable system to probe the role of intrinsic disorder in the assembly of large macromolecular complexes. Broader Impacts: The PI has a strong record of research contributions with undergraduate students, and of mentoring minorities and students with disabilities. The PI is taking a leading role on her campus to introduce molecular biophysics to the research community by providing access to instrumentation and training workshops. Furthermore, the PI will take an active role to promote basic science among high school students by providing opportunities for research lab experience, and by developing instructional material and a hands-on module in the Saturday Academy program. The latter is a highly successful program at Oregon State University for outreach for high school students in which biochemistry and biophysics have not yet been represented.
细胞质动力蛋白是一种基于微管的分子马达,其使用来自ATP水解的能量将细胞货物向微管的负端移动和运输。这种转运在细胞行为的几个方面是必不可少的,包括细胞迁移和分裂,染色体分离和囊泡运输。动力蛋白重链亚基与微管结合并含有提供动力的ATP位点,而轻链和中间链被认为与货物结合并调节马达的活性。来自Barbar实验室的最新数据表明,轻链LC 8的作用是促进动力蛋白中间链的天然无序N-末端结构域的二聚化,而不是如通常认为的那样主要用作货物衔接子。轻链Tctex-1是LC 8的结构同源物,并在与LC 8结合位点相邻的位点结合中间链,可能具有与LC 8相似的作用。该研究项目将测试轻链LC 8和Tctex-1的串联作用是促进动力蛋白组装和与货物适配器dynactin的相互作用,而不是作为货物适配器本身的假设。使用生物物理方法的组合,包括核磁共振光谱(NMR),等温滴定量热法和X射线晶体学,Barbar实验室将阐明两条轻链与动力蛋白中间链相互作用的三个重要结果的机制:1)它们如何有助于形成紧密的动力蛋白组装体,2)它们如何促进中间链的二聚化,以及3)它们如何可能促进中间链与动力肌动蛋白的p150 Glued亚基的更紧密的相互作用。这些轻链的重要作用将在该项目的合作者Tom Hays教授的实验室中进行体内测试。这些研究将为动力蛋白运动功能的结构生物学和热力学提供新的见解,并将补充在细胞内运输领域占主导地位的细胞生物学方法。由于这些研究提供了第一个结构的洞察力的无序到有序的转变中的动力蛋白组装和它的关联与dynactin的作用,他们允许有机会开发一个易于处理的系统来探测的作用,内在的障碍组装的大分子复合物。 更广泛的影响:PI在本科生的研究贡献以及指导少数民族和残疾学生方面有着良好的记录。PI正在她的校园中发挥主导作用,通过提供仪器和培训研讨会向研究界介绍分子生物物理学。此外,PI将通过提供研究实验室体验的机会以及在周六学院课程中开发教学材料和实践模块,在高中生中发挥积极作用,促进基础科学。后者是俄勒冈州州立大学的一个非常成功的项目,旨在为高中生提供生物化学和生物物理学方面的服务。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Elisar Barbar其他文献
Mechanisms Underlying the Binding Diversity of Dynein Light Chain
- DOI:
10.1016/j.bpj.2008.12.2876 - 发表时间:
2009-02-01 - 期刊:
- 影响因子:
- 作者:
Elisar Barbar;Justin Hall;Gregory Benison;Paul A. Karplus;Afua Nyarko - 通讯作者:
Afua Nyarko
Light Chain-Mediated Self-Association of Intrinsically Disordered Dynein Intermediate Chain
- DOI:
10.1016/j.bpj.2009.12.3578 - 发表时间:
2010-01-01 - 期刊:
- 影响因子:
- 作者:
Afua Nyarko;Elisar Barbar - 通讯作者:
Elisar Barbar
Intrinsic Protein Disorder in the Regulation of Large Molecular Machines
- DOI:
10.1016/j.bpj.2012.11.052 - 发表时间:
2013-01-29 - 期刊:
- 影响因子:
- 作者:
Elisar Barbar - 通讯作者:
Elisar Barbar
Multivalency in 53BP1-LC8 interactions suggest new binding mode in LC8 interactions
- DOI:
10.1016/j.bpj.2022.11.1930 - 发表时间:
2023-02-10 - 期刊:
- 影响因子:
- 作者:
Jesse J. Howe;Austin Weeks;Maya Sonpatki;Patrick N. Reardon;Elisar Barbar - 通讯作者:
Elisar Barbar
Elisar Barbar的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Elisar Barbar', 18)}}的其他基金
EAGER: Structure and Assembly of SARS-CoV2 nucleocapsid phosphoprotein N
EAGER:SARS-CoV2 核衣壳磷蛋白 N 的结构和组装
- 批准号:
2034446 - 财政年份:2020
- 资助金额:
$ 78.5万 - 项目类别:
Standard Grant
Structural Basis of Phosphorylation and Alternative Splicing in Dynein Regulation
动力蛋白调节中磷酸化和选择性剪接的结构基础
- 批准号:
1617019 - 财政年份:2016
- 资助金额:
$ 78.5万 - 项目类别:
Continuing Grant
CAREER: Structural Studies of a Highly Conserved Dynein Light Chain and its Role in Dynein Assembly and Cargo Recruitment
职业:高度保守的动力蛋白轻链的结构研究及其在动力蛋白组装和货物招募中的作用
- 批准号:
0417181 - 财政年份:2003
- 资助金额:
$ 78.5万 - 项目类别:
Continuing Grant
CAREER: Structural Studies of a Highly Conserved Dynein Light Chain and its Role in Dynein Assembly and Cargo Recruitment
职业:高度保守的动力蛋白轻链的结构研究及其在动力蛋白组装和货物招募中的作用
- 批准号:
0238094 - 财政年份:2003
- 资助金额:
$ 78.5万 - 项目类别:
Continuing Grant
相似海外基金
Role of Dynein Heavy Chain 3`UTR in the axonal localization and translation of its mRNA
动力蛋白重链 3`UTR 在其 mRNA 轴突定位和翻译中的作用
- 批准号:
23K27107 - 财政年份:2024
- 资助金额:
$ 78.5万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Role of Dynein Heavy Chain 3`UTR in the axonal localization and translation of its mRNA
动力蛋白重链 3`UTR 在其 mRNA 轴突定位和翻译中的作用
- 批准号:
23H02414 - 财政年份:2023
- 资助金额:
$ 78.5万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Elucidating the role of dynein-cargo adaptor proteins in Human papillomavirus infection
阐明动力蛋白-货物衔接蛋白在人乳头瘤病毒感染中的作用
- 批准号:
10726559 - 财政年份:2022
- 资助金额:
$ 78.5万 - 项目类别:
Elucidating the role of dynein-cargo adaptor proteins in Human papillomavirus infection
阐明动力蛋白-货物衔接蛋白在人乳头瘤病毒感染中的作用
- 批准号:
10908071 - 财政年份:2022
- 资助金额:
$ 78.5万 - 项目类别:
Elucidating the role of dynein-cargo adaptor proteins in Human papillomavirus infection
阐明动力蛋白-货物衔接蛋白在人乳头瘤病毒感染中的作用
- 批准号:
10461590 - 财政年份:2022
- 资助金额:
$ 78.5万 - 项目类别:
The Role of Dynein Motor Mutations in Motile Cilia Disease
动力蛋白运动突变在运动纤毛疾病中的作用
- 批准号:
10548220 - 财政年份:2020
- 资助金额:
$ 78.5万 - 项目类别:
The Role of Dynein Motor Mutations in Motile Cilia Disease
动力蛋白运动突变在运动纤毛疾病中的作用
- 批准号:
10367978 - 财政年份:2020
- 资助金额:
$ 78.5万 - 项目类别:
Role of kinesin/dynein adaptor JSAP in reactive oxygen species-induced cell death and lysosome positioning
驱动蛋白/动力蛋白接头 JSAP 在活性氧诱导的细胞死亡和溶酶体定位中的作用
- 批准号:
19K16737 - 财政年份:2019
- 资助金额:
$ 78.5万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Clarifying the role of the cytoplasmic dynein motor complex in polyomavirus nuclear entry.
阐明细胞质动力蛋白运动复合物在多瘤病毒核进入中的作用。
- 批准号:
9758812 - 财政年份:2019
- 资助金额:
$ 78.5万 - 项目类别:
The role of dynein-2 in building a functional cilium.
dynein-2 在构建功能性纤毛中的作用。
- 批准号:
BB/S005390/1 - 财政年份:2019
- 资助金额:
$ 78.5万 - 项目类别:
Research Grant