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Published on: January 20, 2022
THE IMS PARADOX: A PERSPECTIVE ON STRUCTURAL ION MOBILITY-MASS SPECTROMETRY
Jacob W McCabe1, Michael J Hebert1, Mehdi Shirzadeh1
1Department of Chemistry, Texas A&M University, College Station, TX, 77843.
Advancements in ion mobility-mass spectrometry (IM-MS) enhance structural analysis of large protein complexes. New Fourier-transform IM-MS instruments provide high resolution for gas-phase ion structures, revealing conformational heterogeneity.
Area of Science:
- Biochemistry
- Analytical Chemistry
- Structural Biology
Background:
- Studying large proteins and complexes requires higher resolution in ion mobility (IM) and mass spectrometry (MS).
- Ion mobility-mass spectrometry (IM-MS) is crucial for analyzing these large biomolecules.
- The retention of solution-phase structures in gas-phase ions is a key consideration for structural analysis.
Purpose of the Study:
- To review evolutionary developments in IM-MS for enhanced structural analysis of large proteins and complexes.
- To highlight the utility of Fourier-transform IM-MS instruments for structural determination.
- To discuss the ability of IM-MS to analyze conformationally heterogeneous systems.
Main Methods:
- Development of Fourier-transform ion mobility-mass spectrometry (IM-MS) instruments.
- Integration of drift tube (DT) ion mobility with high-resolution orbitrap mass spectrometry.
- Utilizing native MS/IM-MS capabilities for advanced biomolecular analysis.
Main Results:
- Fourier-transform IM-MS instruments offer enhanced resolution for structural analysis of large proteins and complexes.
- Drift tube ion mobility-mass spectrometry (DT-IMS) enables first-principles determination of collision cross sections (CSS).
- The developed instrument merges DT-IMS with high-mass resolution orbitrap MS, incorporating advanced native MS/IM-MS features.
Conclusions:
- Gas-phase ions can retain solution-phase structures, enabling structural IM-MS.
- IM-MS directly measures conformational entropy in heterogeneous systems.
- The advanced Fourier-transform IM-MS instrument is a significant development for biomolecular structural analysis.
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