Multiplexed mass spectrometry of individual ions improves measurement of proteoforms and their complexes

Jared O Kafader; Rafael D Melani; Kenneth R Durbin; Bon Ikwuagwu; Bryan P Early; Ryan T Fellers; Steven C Beu; Vlad Zabrouskov; Alexander A Makarov; Joshua T Maze; Deven L Shinholt; Ping F Yip; Danielle Tullman-Ercek; Michael W Senko; Philip D Compton; Neil L Kelleher

doi:10.1038/s41592-020-0764-5

Multiplexed mass spectrometry of individual ions improves measurement of proteoforms and their complexes

Nat Methods. 2020 Apr;17(4):391-394. doi: 10.1038/s41592-020-0764-5. Epub 2020 Mar 2.

Authors

Jared O Kafader¹, Rafael D Melani¹, Kenneth R Durbin¹, Bon Ikwuagwu², Bryan P Early¹, Ryan T Fellers¹, Steven C Beu³, Vlad Zabrouskov⁴, Alexander A Makarov⁵, Joshua T Maze⁶, Deven L Shinholt⁶, Ping F Yip⁴, Danielle Tullman-Ercek², Michael W Senko⁴, Philip D Compton⁷, Neil L Kelleher⁸

Affiliations

¹ Departments of Chemistry, Molecular Biosciences, The Chemistry of Life Processes Institute, The Proteomics Center of Excellence at Northwestern University, Evanston, IL, USA.
² Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USA.
³ S.C. Beu Consulting, Austin, TX, USA.
⁴ Thermo Fisher Scientific, San Jose, CA, USA.
⁵ Thermo Fisher Scientific, Bremen, Germany.
⁶ Thermo Fisher Scientific, Austin, TX, USA.
⁷ Departments of Chemistry, Molecular Biosciences, The Chemistry of Life Processes Institute, The Proteomics Center of Excellence at Northwestern University, Evanston, IL, USA. philip-compton@northwestern.edu.
⁸ Departments of Chemistry, Molecular Biosciences, The Chemistry of Life Processes Institute, The Proteomics Center of Excellence at Northwestern University, Evanston, IL, USA. n-kelleher@northwestern.edu.

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 (I²MS) 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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Mass Spectrometry / methods*
Proteins / chemistry*
Proteomics / methods*

Substances

Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding