课题基金 / 基金详情

Mechanisms of small heat shock protein sequestrases

Mechanisms of small heat shock protein sequestrases
小热休克蛋白多价螯合酶的机制
批准号:
461328467
负责人:
Professor Dr. Bernd Bukau
金额:
$0.0万
依托单位国家:
德国
项目类别:
Research Grants
财政年份:
--
资助国家:
德国
项目状态:
未结题
起止时间:

项目摘要

项目成果

Professor Dr. Bernd Bukau的其他基金

相似基金

相关文献

中文摘要
翻译
点击翻译按钮获取中文摘要
英文摘要
The imbalance of protein homeostasis caused by stress conditions or cellular ageing results in the accumulation of misfolded protein species, which is linked to cell toxicity. A sophisticated proteostasis network removes misfolded proteins by their refolding, degradation or sequestration into intracellular inclusions. Sequestration is a protein quality control strategy that has been recognized only recently, and the cellular factors involved, underlying mechanisms and physiological functions of sequestration are just beginning to unfold.Protein sequestration is best characterized in Saccharomyces cerevisiae where it is executed by the Hsp42 and Btn2 sequestrases. Hsp42 is member of the small heat shock protein (sHsp) family and shares common features with Btn2, including the presence of large disordered regions, the ability to self-assemble and to direct bound substrates to Hsp70/Hsp100-dependent refolding pathways. In previous work we investigated the basic mechanism of Hsp42 sequestrase activity, which involves a prion-like domain that binds substrates and a charged, disordered domain that regulates sequestrase activity. Both Hsp42 and Btn2 promote cell survival under conditions of limited Hsp70 availability, presumably because misfolded proteins become secluded into inclusions which frees Hsp70 capacity. This unique phenotype of sequestrase mutants enabled us to set up a screen for C. elegans sequestrases that restore growth and protein sequestration in yeast mutants with lacking sequestrase and limiting Hsp70 activities. Our preliminary experiments identified selected C. elegans sHsps as sequestrases, which contribute to life span of the animals. Other sHsps do not show such activity, indicating functional specialization among sHsps in metazoa. Here, we plan to determine the mechanism of sHsp sequestrases, their physiological relevance in a metazoan and how sequestrases are triaging bound substrates to refolding pathways. Our major research aims are: (1) explore whether sequestration represents a conserved activity of sHsps by testing sHsps from different kingdoms of life in our yeast sequestrase mutant screen; (2) define the biochemical and structural features that underlie sHsp sequestrase activity; (3) determine the physiological role of sequestrase positive sHsps in C. elegans; (4) dissect how sequestrase activity is regulated by environmental cues using Hsp42 as model; (5) determine the structures of sequestrase/substrate complexes by cryo electron tomography and how they are modulated by Hsp70/Hsp100 disaggregases. With these experiments we expect to reveal key mechanisms driving the protein sequestration function of sHsps, which constitutes a prime line of defense of cells against proteotoxic stress.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Analysis of the molecular mechanism of Hsp70 chaperones
  • 批准号:
    183020176
  • 项目类别:
    Research Grants
  • 资助金额:
    $0.0万
  • 财政年份:
    2010
  • 负责人:
    Professor Dr. Bernd Bukau
  • 依托单位:
Functional analysis of enzymes involved in the co-translational modification of nascent chains
Wirkungsweise von molekularen Chaperonen und Proteasen in der Faltung und Degradation von Proteinen im Cytosol
Mechanisms of protease-substrate interactions in the E. coli cytosol
  • 批准号:
    5361995
  • 项目类别:
    Priority Programmes
  • 资助金额:
    $0.0万
  • 财政年份:
    2002
  • 负责人:
    Professor Dr. Bernd Bukau
  • 依托单位:
国内基金
海外基金
昼夜节律性small RNA在血斑形成时间推断中的法医学应用研究
  • 批准号:
  • 项目类别:
    省市级项目
  • 资助金额:
    --
  • 批准年份:
    2024
  • 负责人:
  • 依托单位:
用于小尺寸管道高分辨成像荧光聚合物点的构建、成像机制及应用研究
  • 批准号:
    82372015
  • 项目类别:
    面上项目
  • 资助金额:
    48.00万元
  • 批准年份:
    2023
  • 负责人:
    熊丽琴
  • 依托单位:
新型小分子蛋白—人肝细胞生长因子三环域(hHGFK1)抑制破骨细胞及治疗小鼠骨质疏松的疗效评估与机制研究
  • 批准号:
    82370885
  • 项目类别:
    面上项目
  • 资助金额:
    49.00万元
  • 批准年份:
    2023
  • 负责人:
    姚晨
  • 依托单位:
tRNA-derived small RNA上调YBX1/CCL5通路参与硼替佐米诱导慢性疼痛的机制研究
  • 批准号:
  • 项目类别:
    省市级项目
  • 资助金额:
    10.0万元
  • 批准年份:
    2022
  • 负责人:
    张祥忠
  • 依托单位: