Multiplexed mass spectrometry of individual ions improves measurement of proteoforms and their complexes
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Abstract
An Orbitrap-based ion analysis procedure determines the direct charge for numerous individual protein ions to generate true mass spectra. This individual ion mass spectrometry (I 2 MS) method for charge detection enables the characterization of highly complicated mixtures of proteoforms and their complexes in both denatured and native modes of operation, revealing information not obtainable by typical measurements of ensembles of ions.
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CDMS advantage is analysis of very large biomolecules including virus particles (2.47 MDa) and highly complex intact protein mixtures.
“The major advantage of CDMS is the analysis of very large biomolecules including virus particles (2.47 MDa) and highly complex intact protein mixtures [108,109].”
From Top-down proteomics: challenges, innovations, and applications in basic and clinical research (2020) · cites this paper as [108]
CDMS is one of the most important recent developments for top-down proteomics.
“Arguably, one of the most important recent developments is charge detection mass spectrometry (CDMS) (also referred to as individual ion MS) for top-down proteomics [107–110].”
From Top-down proteomics: challenges, innovations, and applications in basic and clinical research (2020) · cites this paper as [108]
Charge detection MS of noncovalent complexes on Orbitrap instruments allows highly repeatable mass measurement of individual ions.
“In these experiments, small numbers of ions were allowed in the trap, allowing highly repeatable mass measurement of individual ions.”
From Higher-order structural characterisation of native proteins and complexes by top-down mass spectrometry (2020) · cites this paper as [48]
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Self-citationMeasurement of Individual Ions Sharply Increases the Resolution of Orbitrap Mass Spectra of Proteins
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- Authors
- Kafader, J. O., Melani, R. D., Durbin, K. R., Ikwuagwu, B., Early, B. P., Fellers, R. T., Beu, S. C., Zabrouskov, V., Makarov, A. A., Maze, J. T., Shinholt, D. L., Yip, P. F., Tullman-Ercek, D., Senko, M. W., Compton, P. D., & Kelleher, N. L.
- Affiliations
- Northwestern University (US)
- Thermo Fisher Scientific (United States) (US)
- Thermo Fisher Scientific (Germany) (DE)
- Corresponding author
- Compton, Philip D.
- Kelleher, Neil L.
- ORCID
- Venue
- Nature Methods
- Published
- 2020-03-02
- Volume
- 17
- Issue
- 4
- Pages
- 391-394
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- PMC
- PMC7131870
- OpenAlex
- W3009899209
- Cited by
- 197
- References
- 26
- Citations by year
- 2026: 24 · 2025: 26 · 2024: 41 · 2023: 25 · 2022: 32 · 2021: 33 · 2020: 14 · 2019: 1
- FWCI
- 9.92
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Methods (publishedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | NIH Office of the Director (S10OD025194)
- Thermo Fisher Scientific Intensifying Innovation Program
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- proteoforms, protein complexes, charge detection, Orbitrap, native mass spectrometry, denatured state, charge assignment, protein mixtures
- MeSH terms
- Humans, Proteins, Mass Spectrometry, Proteomics
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