Membrane Protein Folding and Assembly

膜蛋白折叠和组装

基本信息

  • 批准号:
    10411888
  • 负责人:
  • 金额:
    $ 39.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-06-01 至 2026-04-30
  • 项目状态:
    未结题

项目摘要

Save date: 15 Jan 2020, 22:40 ABSTRACT Membrane Protein Folding and Assembly Many human diseases, such as cystic fibrosis, result from misfolding of membrane proteins (MPs) during their synthesis and targeting. It is therefore important to understand the principles and mechanism of MP folding and assembly. A largely unexplored part of the problem is to understand folding in the context of the cellular milieu. Toward that goal, we are studying the targeting, secretion, and insertion of membrane proteins along the so-called SecA post- translational pathway of living Escherichia coli. We have shown that the SecA motor ATPase, a significant drug target, can insert single-span membrane proteins (S-SMPs) across the E. coli inner membrane. This simplified in vivo model system eliminates the many unanswered questions about the folding of multi-span MPs along the signal recognition particle (SRP) pathway, because we gain direct access to the translocon-bilayer partitioning process. We have engineered two different chimeric protein families for probing systematically S- SMP stability using TM segments of the form GGPG-H-GPGG (used in an earlier study to determine a biological hydrophobicity scale using a cell-free eukaryotic system). To determine stabilities, we have developed methods for cleaving TM segments in vivo via native intramembrane proteases. We have discovered that many S-SMPs are stable across the membrane only because their periplasmic & cytoplasmic domains cannot cross the membrane. We have also discovered that translocon-to-membrane transfer energetics are not equal to membrane-to-cytoplasm transfer energetics and that stability depends upon growth temperature. An important aspect of our work is the use of Molecular Dynamics simulations in concert with experiments to understand the dynamics of the SecYEG translocon. Little is known about SecA function at the atomic level despite hundreds of papers on the subject. Calling upon our lab’s expertise in lipid-protein interactions, we have laid the foundation for electron cryomicroscopic (cryo-EM) studies of the structure of SecA bound to lipid nanodiscs. Our ambition is to obtain a complete structural view of the SecA-guided secretion process. SWhite_Abstract_MIRA_2020.docx, 15 January 2020
保存日期:2020年1月15日22:40

项目成果

期刊论文数量(0)
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STEPHEN H. WHITE其他文献

STEPHEN H. WHITE的其他文献

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{{ truncateString('STEPHEN H. WHITE', 18)}}的其他基金

Membrane Protein Folding and Assembly
膜蛋白折叠和组装
  • 批准号:
    10612983
  • 财政年份:
    2021
  • 资助金额:
    $ 39.25万
  • 项目类别:
Making Sense of Voltage Sensors
理解电压传感器
  • 批准号:
    8025961
  • 财政年份:
    2009
  • 资助金额:
    $ 39.25万
  • 项目类别:
Making Sense of Voltage Sensors
理解电压传感器
  • 批准号:
    7766185
  • 财政年份:
    2009
  • 资助金额:
    $ 39.25万
  • 项目类别:
Making Sense of Voltage Sensors
理解电压传感器
  • 批准号:
    8214529
  • 财政年份:
    2009
  • 资助金额:
    $ 39.25万
  • 项目类别:
Proj 2:Neutron Diffraction Studies of Voltage Sensor Molecules in Lipid Bilayers
项目 2:脂质双层中电压传感器分子的中子衍射研究
  • 批准号:
    7625288
  • 财政年份:
    2009
  • 资助金额:
    $ 39.25万
  • 项目类别:
Making Sense of Voltage Sensors
理解电压传感器
  • 批准号:
    8435413
  • 财政年份:
    2009
  • 资助金额:
    $ 39.25万
  • 项目类别:
Making Sense of Voltage Sensors
理解电压传感器
  • 批准号:
    7569070
  • 财政年份:
    2009
  • 资助金额:
    $ 39.25万
  • 项目类别:
Membrane protein folding and assembly
膜蛋白折叠和组装
  • 批准号:
    8392280
  • 财政年份:
    2006
  • 资助金额:
    $ 39.25万
  • 项目类别:
Membrane protein folding and assembly
膜蛋白折叠和组装
  • 批准号:
    8197738
  • 财政年份:
    2006
  • 资助金额:
    $ 39.25万
  • 项目类别:
Membrane Protein Folding and Assembly
膜蛋白折叠和组装
  • 批准号:
    7586269
  • 财政年份:
    2006
  • 资助金额:
    $ 39.25万
  • 项目类别:

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Multi-scale stochastic systems motivated by biological models
由生物模型驱动的多尺度随机系统
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    RGPIN-2015-06573
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    2019
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    $ 39.25万
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    Discovery Grants Program - Individual
A Portable low-cost, Point of Investigation CapCell Scope to Image and Quantify the Major Axes of Metabolism and the Associated Vasculature in In vitro and In vivo Biological Models
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