Folding and Chaperone Interactions of Multi-domain Proteins

多结构域蛋白质的折叠和分子伴侣相互作用

基本信息

  • 批准号:
    10662086
  • 负责人:
  • 金额:
    $ 20.6万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-02-01 至 2026-01-31
  • 项目状态:
    未结题

项目摘要

Project Summary Combining several functional units, termed domains, into a single polypeptide chain is a common evolutionary strategy for creating biological complexity. The resulting multi-domain proteins are prevalent in all proteomes and carry out essential cellular functions. However, the increased functional complexity of these large proteins complicates their folding into native functional structures. In contrast to many smaller proteins or individual domains, multi-domain proteins are prone to misfolding and potentially cytotoxic aggregation. In the cell, several factors ensure efficient folding. Folding begins co- translationally, while the ribosome still synthesizes the polypeptide. Molecular chaperones begin to interact with the nascent multi-domain protein as soon as it emerges from the ribosome. Co- translational folding and chaperone interactions are recognized as crucial for efficient multi-domain protein folding. However, these processes remain poorly defined at the molecular level, because it is technically challenging to study them. The goal of this project is to define principles of co-translational folding and chaperone function to better understand how complex multi-domain proteins robustly reach their functional structures. We are using a combination of single-molecule biophysics and live-cell experiments to accomplish this goal. With optical tweezers, we are studying the folding pathways of nascent multi-domain proteins at the single-molecule level. Manipulation of individual molecules is ideally suited to resolve complex folding pathways of nascent proteins, elucidate the contributions of the ribosome and molecular chaperones to the folding process, and determine how co-translational folding and protein synthesis are coupled and regulated to ensure robust outcomes. These detailed in vitro studies are complemented by experiments in live cells that detect co-translational folding events in multi-domain proteins. Protein misfolding and aggregation, misregulation of protein synthesis and decline of chaperone function are hallmarks of many aging-related diseases. Our studies may ultimately provide a mechanistic basis for discovering novel therapeutic strategies to treat some of these diseases.
项目总结

项目成果

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Christian Kaiser其他文献

Christian Kaiser的其他文献

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{{ truncateString('Christian Kaiser', 18)}}的其他基金

Molecular Origins of Neurodegeneration through Force Detangling of Toxic RNA
通过强制解开有毒 RNA 导致神经退行性变的分子起源
  • 批准号:
    10667873
  • 财政年份:
    2023
  • 资助金额:
    $ 20.6万
  • 项目类别:
Folding and Chaperone Interactions of Multi-domain Proteins
多结构域蛋白质的折叠和分子伴侣相互作用
  • 批准号:
    10446687
  • 财政年份:
    2017
  • 资助金额:
    $ 20.6万
  • 项目类别:
Single-molecule studies of Sec-dependent protein translocation
Sec 依赖性蛋白质易位的单分子研究
  • 批准号:
    9374906
  • 财政年份:
    2017
  • 资助金额:
    $ 20.6万
  • 项目类别:
Folding and chaperone interactions of multi-domain proteins
多结构域蛋白质的折叠和分子伴侣相互作用
  • 批准号:
    9217889
  • 财政年份:
    2017
  • 资助金额:
    $ 20.6万
  • 项目类别:
Single molecule analysis of nascent protein folding
新生蛋白质折叠的单分子分析
  • 批准号:
    7570874
  • 财政年份:
    2008
  • 资助金额:
    $ 20.6万
  • 项目类别:
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