Innovative Native Ion Mobility Approaches for Transformational Measurements in Structural Biology

用于结构生物学转化测量的创新天然离子淌度方法

基本信息

  • 批准号:
    10689746
  • 负责人:
  • 金额:
    $ 28.77万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-05 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

Project Summary Advancements in biophysical techniques, such as X-ray and cryoEM, have undoubtedly accelerated determination of protein structure. However, it still remains challenging to capture snapshots of protein folding intermediates, including non-native states, and breathing motions that protein assemblies undergo to perform their biological function. Moreover, understanding how molecules, such as lipids, modulate protein structure and function is of paramount biological importance. Over the past two decades, mass spectrometry (MS) of intact protein complexes, often referred to as native MS, has emerged as an indispensable biophysical technique whereby non-covalent interactions and protein structure are preserved within the mass spectrometer. Native MS is a rapid and sensitive technique that has already provided invaluable information on subunit stoichiometry and topology, allostery and cooperativity for individual ligand binding events, including their binding thermodynamics. The coupling with ion mobility (IM), a separation technique based on molecule charge and shape, further enhances the capabilities of native MS where it has enabled collision cross section (CCS) measurements for large protein complexes, identification of different conformations for peptides and stabilizing ligands using collision induced unfolding, and insight in folded and denatured structure(s) of proteins. However, low- resolution commercial IM-MS instrumentation has not changed since its introduction 12 years ago. Herein, this proposal seeks to develop transformative native IM-MS technologies with high-resolution IM and MS capabilities that can address modern questions in structural biology, such as conformational dynamics, including those that may have remained “hidden”, within membrane transporters under turnover conditions. In order to achieve these transformative goals, an interdisciplinary team of researchers whose expertise spans the fields of protein biophysics, expression and purification of proteins inclusive of membrane proteins, as well as traditional protein structure characterization, such as X-ray crystallography, has been assembled. Team members also possess decades of experience in the field of mass spectrometry inclusive of fundamental ion chemistry/physics, seminal contributions that have spawned MS proteomics, and related areas of analytical mass spectrometry and ion mobility- mass spectrometry. Collectively, the background and expertise of this research team is uniquely positioned to transform the field of IM-MS in the area of structural biology. In short, the proposed transformative research will lead to forefront IM-MS instrumentation that is poised to provide unprecedented insights into the structure and assembly of protein complexes and push the field into new frontiers of research.
项目总结

项目成果

期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Considerations for Generating Frequency Modulation Waveforms for Fourier Transform-Ion Mobility Experiments.
Synchronized Stepped Frequency Modulation for Multiplexed Ion Mobility Measurements.
Nonlinear Frequency Modulation for Fourier Transform Ion Mobility Mass Spectrometry Improves Experimental Efficiency.
傅里叶变换离子淌度质谱的非线性频率调制提高了实验效率。
  • DOI:
    10.1016/j.ijms.2024.117197
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    1.8
  • 作者:
    Cabrera,ElvinR;Schrader,RobertL;Walker,ThomasE;Laganowsky,Arthur;Russell,DavidH;Clowers,BrianH
  • 通讯作者:
    Clowers,BrianH
Masked Multiplexed Separations to Enhance Duty Cycle for Structures for Lossless Ion Manipulations.
  • DOI:
    10.1021/acs.analchem.0c04799
  • 发表时间:
    2021-04-13
  • 期刊:
  • 影响因子:
    7.4
  • 作者:
    Clowers BH;Cabrera E;Anderson G;Deng L;Moser K;Van Aken G;DeBord JD
  • 通讯作者:
    DeBord JD
Absorption Mode Fourier Transform Ion Mobility Mass Spectrometry Multiplexing Combined with Half-Window Apodization Windows Improves Resolution and Shortens Acquisition Times.
  • DOI:
    10.1021/acs.analchem.1c01427
  • 发表时间:
    2021-07-13
  • 期刊:
  • 影响因子:
    7.4
  • 作者:
    Sanders, James D.;Butalewicz, Jamie P.;Clowers, Brian H.;Brodbelt, Jennifer S.
  • 通讯作者:
    Brodbelt, Jennifer S.
{{ 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 }}

Brian Clowers其他文献

Brian Clowers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('Brian Clowers', 18)}}的其他基金

Tractable Tandem Ion Mobility Technology using Structures for Lossless Ion Manipulations and Photodissociation
使用无损离子操作和光解离结构的易处理串联离子淌度技术
  • 批准号:
    10386669
  • 财政年份:
    2021
  • 资助金额:
    $ 28.77万
  • 项目类别:
Tractable Tandem Ion Mobility Technology using Structures for Lossless Ion Manipulations and Photodissociation
使用无损离子操作和光解离结构的易处理串联离子淌度技术
  • 批准号:
    10322113
  • 财政年份:
    2021
  • 资助金额:
    $ 28.77万
  • 项目类别:
Tractable Tandem Ion Mobility Technology using Structures for Lossless Ion Manipulations and Photodissociation
使用无损离子操作和光解离结构的易处理串联离子淌度技术
  • 批准号:
    10548229
  • 财政年份:
    2021
  • 资助金额:
    $ 28.77万
  • 项目类别:
Innovative Native Ion Mobility Approaches for Transformational Measurements in Structural Biology
用于结构生物学转化测量的创新天然离子淌度方法
  • 批准号:
    10042584
  • 财政年份:
    2020
  • 资助金额:
    $ 28.77万
  • 项目类别:
Innovative Native Ion Mobility Approaches for Transformational Measurements in Structural Biology
用于结构生物学转化测量的创新天然离子淌度方法
  • 批准号:
    10252003
  • 财政年份:
    2020
  • 资助金额:
    $ 28.77万
  • 项目类别:
Innovative Native Ion Mobility Approaches for Transformational Measurements in Structural Biology
用于结构生物学转化测量的创新天然离子淌度方法
  • 批准号:
    10477459
  • 财政年份:
    2020
  • 资助金额:
    $ 28.77万
  • 项目类别:

相似海外基金

ATP Binding Cassette Transporters in Health and Disease
健康和疾病中的 ATP 结合盒转运蛋白
  • 批准号:
    10390366
  • 财政年份:
    2021
  • 资助金额:
    $ 28.77万
  • 项目类别:
ATP Binding Cassette Transporters in Health and Disease
健康和疾病中的 ATP 结合盒转运蛋白
  • 批准号:
    10237095
  • 财政年份:
    2021
  • 资助金额:
    $ 28.77万
  • 项目类别:
ATP Binding Cassette Transporters in Health and Disease
健康和疾病中的 ATP 结合盒转运蛋白
  • 批准号:
    10552563
  • 财政年份:
    2021
  • 资助金额:
    $ 28.77万
  • 项目类别:
Photosensitizing Nanoconstructs for Regulation of ATP-Binding Cassette Transporters in the Brain
用于调节大脑中 ATP 结合盒转运蛋白的光敏纳米结构
  • 批准号:
    2030253
  • 财政年份:
    2020
  • 资助金额:
    $ 28.77万
  • 项目类别:
    Standard Grant
Structural and functional studies of iron uptake ATP-binding cassette transporters (ABC transporters) in Gram-negative bacteria
革兰氏阴性菌中铁摄取 ATP 结合盒转运蛋白(ABC 转运蛋白)的结构和功能研究
  • 批准号:
    20K22561
  • 财政年份:
    2020
  • 资助金额:
    $ 28.77万
  • 项目类别:
    Grant-in-Aid for Research Activity Start-up
Investigating the mechanism of polysaccharide recognition and export by bacterial ATP-binding cassette transporters
研究细菌 ATP 结合盒转运蛋白识别和输出多糖的机制
  • 批准号:
    489384-2016
  • 财政年份:
    2018
  • 资助金额:
    $ 28.77万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Investigating the mechanism of polysaccharide recognition and export by bacterial ATP-binding cassette transporters
研究细菌 ATP 结合盒转运蛋白识别和输出多糖的机制
  • 批准号:
    489384-2016
  • 财政年份:
    2017
  • 资助金额:
    $ 28.77万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Investigating the mechanism of polysaccharide recognition and export by bacterial ATP-binding cassette transporters
研究细菌 ATP 结合盒转运蛋白识别和输出多糖的机制
  • 批准号:
    489384-2016
  • 财政年份:
    2016
  • 资助金额:
    $ 28.77万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Doctoral
The Mechanism of ATP Binding Cassette Transporters
ATP 结合盒转运蛋白的机制
  • 批准号:
    318360
  • 财政年份:
    2014
  • 资助金额:
    $ 28.77万
  • 项目类别:
    Fellowship Programs
Heat shock protein 27 attenuates foam cell formation by enhancing cholesterol efflux via the ATP-binding cassette transporters A1
热休克蛋白 27 通过 ATP 结合盒转运蛋白 A1 增强胆固醇流出,从而减弱泡沫细胞形成
  • 批准号:
    304334
  • 财政年份:
    2014
  • 资助金额:
    $ 28.77万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了