Isotopic Resolution of Protein Complexes up to 466 kDa Using Individual Ion Mass Spectrometry

John P. McGee, Rafael D. Melani, Ping F. Yip, Michael W. Senko, Philip D. Compton, Jared O. Kafader, Neil L. Kelleher*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Native mass spectrometry involves transferring large biomolecular complexes into the gas phase, enabling the characterization of their composition and stoichiometry. However, the overlap in distributions created by residual solvation, ionic adducts, and post-translational modifications creates a high degree of complexity that typically goes unresolved at masses above ∼150 kDa. Therefore, native mass spectrometry would greatly benefit from higher resolution approaches for intact proteins and their complexes. By recording mass spectra of individual ions via charge detection mass spectrometry, we report isotopic resolution for pyruvate kinase (232 kDa) and β-galactosidase (466 kDa), extending the limits of isotopic resolution for high mass and high m/z by >2.5-fold and >1.6-fold, respectively.

Original languageEnglish (US)
JournalAnalytical Chemistry
Issue number5
StatePublished - Feb 9 2021

ASJC Scopus subject areas

  • Analytical Chemistry


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