Systematic Analysis of the Regulation of Hsp90 by its cofactors

Hsp90 辅因子调控的系统分析

基本信息

  • 批准号:
    238282-2012
  • 负责人:
  • 金额:
    $ 1.89万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2012
  • 资助国家:
    加拿大
  • 起止时间:
    2012-01-01 至 2013-12-31
  • 项目状态:
    已结题

项目摘要

Protein homeostasis in the cell is regulated by a wide array of molecular systems consisting of molecular chaperones and proteases. These systems ensure that proteins fold to their native state and maintain their proper conformation throughout their lifetime in the cell. The chaperone surveillance systems also ensure that misfolded proteins and short-lived regulatory proteins are targeted for degradation. Hsp90 is one of the major and most highly conserved chaperones of the cell that functions to assist proteins in attaining their active conformation. Hsp90 has also been found to be involved in protein degradation. It is an ATP-dependent chaperone that forms a constitutive dimer, which exhibits multiple conformations regulated by ATP binding and hydrolysis. The in vivo and in vitro activity of Hsp90 is controlled by a large number of cofactors that target the chaperone to specific substrates. Well-established Hsp90 cofactors in yeast include: Sti1 (Hop), Sba1 (p23), Cdc37 (p50), Cpr6, Cpr7, Cns1, Aha1, Hch1, and Ppt1. Hsp90 forms specific complexes with these cofactors and target substrates. Knowledge of the composition and relative function of each of these different Hsp90-cofactor complexes is still fragmentary and has come largely from reconstitution experiments using partially purified proteins. As a result, the mechanism of Hsp90 function remains elusive due to the dynamic and heterogeneous nature of the chaperone-cofactor-substrate complexes. In this grant application, we propose to carry out a systematic analysis using proteomic and biochemical approaches in order to understand how substrate specificity is established by the Hsp90-cofactor system and, consequently, how the different cofactors regulate Hsp90 activity. To this end, several approaches will be undertaken. (1) Systematic analysis of interactors common to Hsp90 and its cofactors under normal and 'stress' growth conditions will be carried out. (2) The interaction studies will be complimented by extensive computational interrogation of the data to reveal common features that dictate the interaction of a substrate with a specific Hsp90-cofactor complex. (3) Follow up biochemical studies will be carried out to verify the results from the bioinformatic analysis.
细胞中蛋白质的稳态由分子伴侣和蛋白酶组成的广泛的分子系统调节。这些系统确保蛋白质折叠到它们的天然状态,并在它们在细胞中的整个生命周期中保持它们的正确构象。分子伴侣监视系统还确保错误折叠的蛋白质和短寿命的调节蛋白质被靶向降解。Hsp 90是细胞中主要且最高度保守的分子伴侣之一,其功能是帮助蛋白质获得其活性构象。Hsp 90也被发现参与蛋白质降解。它是一种ATP依赖性分子伴侣,形成组成型二聚体,表现出受ATP结合和水解调节的多种构象。Hsp 90的体内和体外活性由大量的辅因子控制,这些辅因子将分子伴侣靶向特定底物。在酵母中已确定的Hsp 90辅因子包括:Sti 1(Hop)、Sba 1(p23)、Cdc 37(p50)、Cpr 6、Cpr 7、Cns 1、Aha 1、Hch 1和Ppt 1。Hsp 90与这些辅因子和靶底物形成特异性复合物。这些不同的热休克蛋白90-辅因子复合物的组成和相对功能的知识仍然是零碎的,主要来自使用部分纯化的蛋白质的重建实验。因此,由于分子伴侣-辅因子-底物复合物的动态和异质性,Hsp 90功能的机制仍然难以捉摸。在这项授权申请中,我们建议使用蛋白质组学和生物化学方法进行系统的分析,以了解底物特异性是如何通过Hsp 90-辅因子系统建立的,因此,不同的辅因子如何调节Hsp 90活性。为此,将采取若干办法。(1)将进行系统分析的相互作用共同的HSP 90和它的辅助因子在正常和“应力”的生长条件下。(2)相互作用的研究将补充广泛的计算询问的数据,揭示共同的特点,决定了一个特定的热休克蛋白90-辅因子复合物的底物的相互作用。(3)将进行后续生化研究,以验证生物信息学分析的结果。

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 }}

Houry, Walid其他文献

Second Virtual International Symposium on Cellular and Organismal Stress Responses, September 8-9, 2022.
  • DOI:
    10.1007/s12192-022-01318-5
  • 发表时间:
    2023-01
  • 期刊:
  • 影响因子:
    3.8
  • 作者:
    van Oosten-Hawle, Patricija;Backe, Sarah J.;Ben-Zvi, Anat;Bourboulia, Dimitra;Brancaccio, Mara;Brodsky, Jeff;Clark, Melody;Colombo, Giorgio;Cox, Marc B.;de los Rios, Paolo;Echtenkamp, Frank;Edkins, Adrienne;Freeman, Brian;Goloubinoff, Pierre;Houry, Walid;Johnson, Jill;LaPointe, Paul;Li, Wei;Mezger, Valerie;Neckers, Len;Nillegoda, Nadinath B.;Prahlad, Veena;Reitzel, Adam;Scherz-Shouval, Ruth;Sistonen, Lea;Tsai, Francis T. F.;Woodford, Mark R.;Mollapour, Mehdi;Truman, Andrew W.
  • 通讯作者:
    Truman, Andrew W.

Houry, Walid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('Houry, Walid', 18)}}的其他基金

Structural and functional analysis of the URI1 prefoldin-like chaperone complex
URI1 前折叠蛋白样伴侣复合物的结构和功能分析
  • 批准号:
    RGPIN-2020-04074
  • 财政年份:
    2022
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Discovery Grants Program - Individual
Structural and functional analysis of the URI1 prefoldin-like chaperone complex
URI1 前折叠蛋白样伴侣复合物的结构和功能分析
  • 批准号:
    RGPIN-2020-04074
  • 财政年份:
    2021
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Discovery Grants Program - Individual
Structural and functional analysis of the URI1 prefoldin-like chaperone complex
URI1 前折叠蛋白样伴侣复合物的结构和功能分析
  • 批准号:
    RGPIN-2020-04074
  • 财政年份:
    2020
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Discovery Grants Program - Individual
Characterization of the structure and stability of human serum albumin isolated using a novel plasma extraction technique****
使用新型血浆提取技术分离人血清白蛋白的结构和稳定性表征****
  • 批准号:
    533721-2018
  • 财政年份:
    2018
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Engage Grants Program
Chaperones and Proteases of the Plasmodium falciparum Parasite
恶性疟原虫寄生虫的伴侣和蛋白酶
  • 批准号:
    RGPIN-2014-05393
  • 财政年份:
    2018
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Discovery Grants Program - Individual
Chaperones and Proteases of the Plasmodium falciparum Parasite
恶性疟原虫寄生虫的伴侣和蛋白酶
  • 批准号:
    RGPIN-2014-05393
  • 财政年份:
    2017
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Discovery Grants Program - Individual
Chaperones and Proteases of the Plasmodium falciparum Parasite
恶性疟原虫寄生虫的伴侣和蛋白酶
  • 批准号:
    RGPIN-2014-05393
  • 财政年份:
    2016
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Discovery Grants Program - Individual
High resolution characterization of macromolecular structure and dynamics
大分子结构和动力学的高分辨率表征
  • 批准号:
    RTI-2017-00714
  • 财政年份:
    2016
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Research Tools and Instruments
Chaperones and Proteases of the Plasmodium falciparum Parasite
恶性疟原虫寄生虫的伴侣和蛋白酶
  • 批准号:
    RGPIN-2014-05393
  • 财政年份:
    2015
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Discovery Grants Program - Individual
Chaperones and Proteases of the Plasmodium falciparum Parasite
恶性疟原虫寄生虫的伴侣和蛋白酶
  • 批准号:
    RGPIN-2014-05393
  • 财政年份:
    2014
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Discovery Grants Program - Individual

相似国自然基金

Scalable Learning and Optimization: High-dimensional Models and Online Decision-Making Strategies for Big Data Analysis
  • 批准号:
  • 批准年份:
    2024
  • 资助金额:
    万元
  • 项目类别:
    合作创新研究团队
Intelligent Patent Analysis for Optimized Technology Stack Selection:Blockchain BusinessRegistry Case Demonstration
  • 批准号:
  • 批准年份:
    2024
  • 资助金额:
    万元
  • 项目类别:
    外国学者研究基金项目
基于Meta-analysis的新疆棉花灌水增产模型研究
  • 批准号:
    41601604
  • 批准年份:
    2016
  • 资助金额:
    22.0 万元
  • 项目类别:
    青年科学基金项目
大规模微阵列数据组的meta-analysis方法研究
  • 批准号:
    31100958
  • 批准年份:
    2011
  • 资助金额:
    20.0 万元
  • 项目类别:
    青年科学基金项目
用“后合成核磁共振分析”(retrobiosynthetic NMR analysis)技术阐明青蒿素生物合成途径
  • 批准号:
    30470153
  • 批准年份:
    2004
  • 资助金额:
    22.0 万元
  • 项目类别:
    面上项目

相似海外基金

Systematic Analysis Of Small RNA-Based Regulation Of Gene Expression In Bacteria
细菌中基于小 RNA 的基因表达调控的系统分析
  • 批准号:
    10392065
  • 财政年份:
    2021
  • 资助金额:
    $ 1.89万
  • 项目类别:
Collaborative Research: DMS/NIGMS 2: Methods for Systematic Analysis of Post-transcriptional Regulation in Single Cells
合作研究:DMS/NIGMS 2:单细胞转录后调控的系统分析方法
  • 批准号:
    10378378
  • 财政年份:
    2021
  • 资助金额:
    $ 1.89万
  • 项目类别:
Collaborative Research: DMS/NIGMS 2: Methods for Systematic Analysis of Post-transcriptional Regulation in Single Cells
合作研究:DMS/NIGMS 2:单细胞转录后调控的系统分析方法
  • 批准号:
    10492773
  • 财政年份:
    2021
  • 资助金额:
    $ 1.89万
  • 项目类别:
Collaborative Research: DMS/NIGMS 2: Methods for Systematic Analysis of Post-transcriptional Regulation in Single Cells
合作研究:DMS/NIGMS 2:单细胞转录后调控的系统分析方法
  • 批准号:
    10708803
  • 财政年份:
    2021
  • 资助金额:
    $ 1.89万
  • 项目类别:
Extended fetal monitoring by systematic analysis of fetal autonomic cardiovascular regulation
通过系统分析胎儿自主心血管调节来扩展胎儿监测
  • 批准号:
    375203892
  • 财政年份:
    2017
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Research Grants
Systematic analysis of small RNA-based regulation of gene expression in bacteria
基于小RNA的细菌基因表达调控的系统分析
  • 批准号:
    9212943
  • 财政年份:
    2017
  • 资助金额:
    $ 1.89万
  • 项目类别:
The analysis of systematic gene regulation in skeletal muscle differentiation
骨骼肌分化的系统基因调控分析
  • 批准号:
    26290064
  • 财政年份:
    2014
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Systematic analysis of post-translational regulation of autophagy protease ATG4B
自噬蛋白酶ATG4B翻译后调控的系统分析
  • 批准号:
    BB/J015881/1
  • 财政年份:
    2013
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Research Grant
Systematic functional and mechanistic analysis of gene regulation by antisense transcription in Saccharomyces cerevisiae
酿酒酵母反义转录基因调控的系统功能和机制分析
  • 批准号:
    221516128
  • 财政年份:
    2012
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Research Grants
A systematic analysis of the regulation of small G proteins on the Golgi apparatus
小G蛋白对高尔基体调节的系统分析
  • 批准号:
    200496715
  • 财政年份:
    2011
  • 资助金额:
    $ 1.89万
  • 项目类别:
    Research Fellowships
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了