Analysis of Native-Like Proteins and Protein Complexes Using Cation to Anion Proton Transfer Reactions (CAPTR)

Journal of the American Society for Mass Spectrometry
Kenneth J Laszlo, Matthew F Bush

Abstract

Mass spectra of native-like protein complexes often exhibit narrow charge-state distributions, broad peaks, and contributions from multiple, coexisting species. These factors can make it challenging to interpret those spectra, particularly for mixtures with significant heterogeneity. Here we demonstrate the use of ion/ion proton transfer reactions to reduce the charge states of m/z-selected, native-like ions of proteins and protein complexes, a technique that we refer to as cation to anion proton transfer reactions (CAPTR). We then demonstrate that CAPTR can increase the accuracy of charge state assignments and the resolution of interfering species in native mass spectrometry. The CAPTR product ion spectra for pyruvate kinase exhibit ~30 peaks and enable unambiguous determination of the charge state of each peak, whereas the corresponding precursor spectra exhibit ~6 peaks and the assigned charge states have an uncertainty of ±3%. 15+ bovine serum albumin and 21+ yeast enolase dimer both appear near m/z 4450 and are completely unresolved in a mixture. After a single CAPTR event, the resulting product ions are baseline resolved. The separation of the product ions increases dramatically after each subsequent CAPTR event; 12 event...Continue Reading

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Citations

Jul 12, 2016·Journal of the American Chemical Society·Kenneth J LaszloMatthew F Bush
Aug 9, 2016·Journal of the American Society for Mass Spectrometry·Frederik LermyteFrank Sobott
Aug 11, 2016·Journal of the American Society for Mass Spectrometry·James G BonnerRyan R Julian
Mar 17, 2017·The Journal of Physical Chemistry. B·Kenneth J LaszloMatthew F Bush
Mar 18, 2021·Journal of the American Society for Mass Spectrometry·Melanie Cheung See KitIan K Webb
Mar 20, 2019·Journal of the American Society for Mass Spectrometry·John W Patrick, Arthur Laganowsky
Feb 23, 2017·Journal of the American Society for Mass Spectrometry·Kenneth J LaszloMatthew F Bush
Jun 1, 2017·Journal of the American Society for Mass Spectrometry·Sandilya V B GarimellaRichard D Smith
Feb 15, 2017·Analytical Chemistry·Dustin D Holden, Jennifer S Brodbelt
Dec 5, 2020·Analytical Chemistry·Abdirahman M AbdillahiScott A McLuckey
Nov 7, 2019·Analytical Chemistry·David Foreman, Scott A McLuckey
Sep 3, 2021·Chemical Reviews·Amber D Rolland, James S Prell

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