Effective MS-Based Methods for Unraveling Cell Surface Protein Interactions

基于 MS 的有效解开细胞表面蛋白质相互作用的方法

基本信息

  • 批准号:
    10522689
  • 负责人:
  • 金额:
    $ 34.98万
  • 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 2026-04-30
  • 项目状态:
    未结题

项目摘要

SUMMARY The surface of mammalian cells contains many important proteins including receptors and transporters. They regulate numerous cellular events, such as sensing extracellular nutrients, and initiating cell signaling. Frequently, these proteins do not work independently, but cooperate with one another instead to fulfill the tasks. Aberrant protein interactions on the cell surface will impact protein activities and result in human diseases such as cancer. Therefore, it is not sufficient to identify and quantify surface proteins. Systematic investigation of surface protein interactions can aid in an in-depth understanding of protein functions and cellular activities, and provide insights into the molecular mechanisms of human diseases. However, it is extraordinarily challenging to comprehensively analyze protein interactions only on the cell surface. The objective of this project is to develop innovative and effective methods to globally analyze protein interactions on the cell surface, especially direct interactions among low-abundance surface proteins, and apply the methods to study surface proteins and their interaction changes during the epithelial-to-mesenchymal transition (EMT). Guided by strong preliminary data, this objective will be fulfilled by pursuing three specific aims. 1) Effective MS-based methods for global analysis of protein interactions on the cell surface. Through the development of the innovative methods, surface protein interactors will be systematically analyzed. The cleavable cross-linker with a chemical handle will allow for selective enrichment of cross-linked peptides, which will enable us to identify many more direct interactions among low-abundance surface proteins. Furthermore, integrating cleavable detergents into the workflow will increase the coverage of membrane proteins on the cell surface. 2) Radical chemistry-based methods to tag surface proteins for studying their interactions. Based on the fact that the cell surface is covered with glycans, radicals will be generated through the enzymatic oxidation of glycans, and they will be used to quickly tag surface proteins. Radical chemistry-based methods will further increase the coverage of surface proteins and their interactions. More comprehensive analysis of surface proteins and their interactions on the cell surface will be achieved. 3) Quantification of surface glycoproteins and the surface protein interaction remodeling during the EMT. During the EMT, the properties of cells change dramatically, such as cell morphology, cell-cell interactions, and cell mobility, which are often determined by surface proteins. The proposed methods will be applied to comprehensively analyze surface glycoproteins and the surface protein interaction network remodeling during the EMT. The results will unveil the molecular mechanisms of the EMT and the EMT-relevant diseases. Without sample restrictions, the proposed methods can be extensively applied to study surface protein interactions, leading to the identification of surface proteins as disease biomarkers and drug targets.
总结 哺乳动物细胞表面含有许多重要的蛋白质,包括受体和转运蛋白。他们 调节许多细胞事件,如感知细胞外营养物质和启动细胞信号。 通常,这些蛋白质不是独立工作,而是相互合作来完成任务。 细胞表面异常的蛋白质相互作用将影响蛋白质活性并导致人类疾病,例如 癌症因此,仅鉴定和定量表面蛋白是不够的。系统的调查 表面蛋白质相互作用有助于深入了解蛋白质功能和细胞活性, 为人类疾病的分子机制提供了新的见解。然而,这是非常具有挑战性的, 仅在细胞表面全面分析蛋白质相互作用。该项目的目标是开发 创新和有效的方法来全面分析细胞表面上的蛋白质相互作用,特别是直接 低丰度表面蛋白之间的相互作用,并应用该方法研究表面蛋白及其 在上皮-间充质转化(EMT)期间的相互作用变化。在强有力的初步数据的指导下, 为实现这一目标,将努力实现三个具体目标。1)有效的基于MS的全局分析方法 细胞表面蛋白质相互作用。通过创新方法的发展, 将系统地分析互动者。具有化学手柄的可裂解交联剂将允许 交联肽的选择性富集,这将使我们能够识别更多的直接相互作用 低丰度的表面蛋白。此外,将可裂解洗涤剂整合到工作流程中将 增加细胞表面膜蛋白的覆盖。2)基于自由基化学的标记方法 表面蛋白质用于研究它们的相互作用。基于细胞表面覆盖有聚糖的事实, 通过聚糖的酶促氧化将产生自由基,它们将用于快速标记表面 proteins.基于自由基化学的方法将进一步增加表面蛋白质的覆盖率及其在生物医学中的应用。 交互.对细胞表面蛋白及其相互作用的更全面的分析将在 办妥了一批3)表面糖蛋白的定量和表面蛋白质相互作用重塑过程中 急救员在EMT过程中,细胞的特性发生了巨大的变化,如细胞形态,细胞间相互作用, 和细胞移动性,这通常由表面蛋白决定。所提出的方法将适用于 全面分析了表面糖蛋白和表面蛋白相互作用网络的重塑过程中, 急救人员研究结果将揭示EMT及其相关疾病的分子机制。没有 样品限制,所提出的方法可以广泛应用于研究表面蛋白质相互作用, 从而鉴定出表面蛋白作为疾病生物标志物和药物靶点。

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 }}

Ronghu Wu其他文献

Ronghu Wu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('Ronghu Wu', 18)}}的其他基金

Capturing Low-Abundance Glycopeptides for Decoding the Glycoproteome
捕获低丰度糖肽以解码糖蛋白组
  • 批准号:
    10260575
  • 财政年份:
    2020
  • 资助金额:
    $ 34.98万
  • 项目类别:
Capturing Low-Abundance Glycopeptides for Decoding the Glycoproteome
捕获低丰度糖肽以解码糖蛋白组
  • 批准号:
    10440467
  • 财政年份:
    2020
  • 资助金额:
    $ 34.98万
  • 项目类别:
Capturing Low-Abundance Glycopeptides for Decoding the Glycoproteome
捕获低丰度糖肽以解码糖蛋白组
  • 批准号:
    10669037
  • 财政年份:
    2020
  • 资助金额:
    $ 34.98万
  • 项目类别:
Supplemental Funds for a Thermo Scientific Q Exactive HF Mass Spectrometer
Thermo Scientific Q Exactive HF 质谱仪的补充资金
  • 批准号:
    10384259
  • 财政年份:
    2020
  • 资助金额:
    $ 34.98万
  • 项目类别:
Effective MS-Based Methods for Unraveling Cell Surface Protein Interactions
基于 MS 的有效解开细胞表面蛋白质相互作用的方法
  • 批准号:
    10671551
  • 财政年份:
    2017
  • 资助金额:
    $ 34.98万
  • 项目类别:
Effective Methods to Globally Analyze Cell Surface Proteins and Glycoproteins
全面分析细胞表面蛋白和糖蛋白的有效方法
  • 批准号:
    9239644
  • 财政年份:
    2017
  • 资助金额:
    $ 34.98万
  • 项目类别:
Effective Methods to Globally Analyze Cell Surface Proteins and Glycoproteins
全面分析细胞表面蛋白和糖蛋白的有效方法
  • 批准号:
    9417031
  • 财政年份:
    2017
  • 资助金额:
    $ 34.98万
  • 项目类别:

相似海外基金

How lipid binding proteins shape the activity of nuclear hormone receptors
脂质结合蛋白如何影响核激素受体的活性
  • 批准号:
    DP240103141
  • 财政年份:
    2024
  • 资助金额:
    $ 34.98万
  • 项目类别:
    Discovery Projects
Structural classification of NHEJ pathways; unravelling the role of Ku-binding proteins
NHEJ通路的结构分类;
  • 批准号:
    MR/X00029X/1
  • 财政年份:
    2023
  • 资助金额:
    $ 34.98万
  • 项目类别:
    Research Grant
BRC-BIO: Evolutionary Patterns of Ice-Binding Proteins in North Pacific Intertidal Invertebrates
BRC-BIO:北太平洋潮间带无脊椎动物冰结合蛋白的进化模式
  • 批准号:
    2312378
  • 财政年份:
    2023
  • 资助金额:
    $ 34.98万
  • 项目类别:
    Standard Grant
Exploring the roles and functions of sex steroid hormone receptor-associated RNA binding proteins in the development of geriatric diseases.
探索性类固醇激素受体相关 RNA 结合蛋白在老年疾病发展中的作用和功能。
  • 批准号:
    23K06408
  • 财政年份:
    2023
  • 资助金额:
    $ 34.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
UV Plasmon-Enhanced Chiroptical Spectroscopy of Membrane-Binding Proteins
膜结合蛋白的紫外等离子增强手性光谱
  • 批准号:
    10680969
  • 财政年份:
    2023
  • 资助金额:
    $ 34.98万
  • 项目类别:
Investigating physiologic and pathophysiologic connections between the Parkinson's disease protein alpha-synuclein and RNA binding proteins
研究帕金森病蛋白 α-突触核蛋白和 RNA 结合蛋白之间的生理和病理生理联系
  • 批准号:
    10744556
  • 财政年份:
    2023
  • 资助金额:
    $ 34.98万
  • 项目类别:
Structural and computational analysis of immune-related RNA-binding proteins
免疫相关 RNA 结合蛋白的结构和计算分析
  • 批准号:
    23K06597
  • 财政年份:
    2023
  • 资助金额:
    $ 34.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Characterization of carbohydrate-binding proteins and their applications
碳水化合物结合蛋白的表征及其应用
  • 批准号:
    23K05034
  • 财政年份:
    2023
  • 资助金额:
    $ 34.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A machine learning approach to identify carbon dioxide-binding proteins for sustainability and health
一种机器学习方法来识别二氧化碳结合蛋白以实现可持续发展和健康
  • 批准号:
    2838427
  • 财政年份:
    2023
  • 资助金额:
    $ 34.98万
  • 项目类别:
    Studentship
The role of RNA binding proteins in heart development and congenital heart defects
RNA结合蛋白在心脏发育和先天性心脏缺陷中的作用
  • 批准号:
    10827567
  • 财政年份:
    2023
  • 资助金额:
    $ 34.98万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了