Ultra-Accurate Correlation Between Precursor and Fragment Ions in Two-Dimensional Mass Spectrometry: Acetylated Vs Trimethylated Histone Peptides

Overview

Journal J Am Soc Mass Spectrom

Specialty Chemistry

Date 2023 Mar 17

PMID 36930827

Authors

Michael Palasser

Sarah V Heel

Marc-Andre Delsuc

Kathrin Breuker

Maria A van Agthoven

Affiliations

Soon will be listed here.

Abstract

Two-dimensional mass spectrometry (2D MS) is a method for tandem mass spectrometry in which precursor and fragment ions are correlated by manipulating ion radii rather than by ion isolation. A 2D mass spectrum contains the fragmentation patterns of all analytes in a sample, acquired in parallel. We report ultrahigh-resolution narrowband 2D mass spectra of a mixture of two histone peptides with the same sequence, one of which carries an acetylation and the other a trimethylation (/ 0.006 difference). We reduced the distance between data points in the precursor ion dimension and compared the accuracy of the precursor-fragment correlation with the resolving power. We manage to perform label-free quantification on the histone peptide mixture and show that precursor and fragment ions can be accurately correlated even though the precursor ions are not resolved. Finally, we show that increasing the resolution of a 2D mass spectrum in the precursor ion dimension too far can lead to a decline in the signal-to-noise ratio.

Citing Articles

Top-Down Proteoform Analysis by 2D MS with Quadrupolar Detection.

Polak M, Palasser M, Kadek A, Kavan D, Wootton C, Delsuc M Anal Chem. 2023; 95(44):16123-16130.

PMID: 37877738 PMC: 10633810. DOI: 10.1021/acs.analchem.3c02225.

References

Floris F, van Agthoven M, Chiron L, Soulby A, Wootton C, Lam Y . 2D FT-ICR MS of Calmodulin: A Top-Down and Bottom-Up Approach. J Am Soc Mass Spectrom. 2016; 27(9):1531-8. DOI: 10.1007/s13361-016-1431-z. View

Simon H, van Agthoven M, Lam P, Floris F, Chiron L, Delsuc M . Uncoiling collagen: a multidimensional mass spectrometry study. Analyst. 2015; 141(1):157-65. DOI: 10.1039/c5an01757b. View

Qi Y, Witt M, Jertz R, Baykut G, Barrow M, N Nikolaev E . Absorption-mode spectra on the dynamically harmonized Fourier transform ion cyclotron resonance cell. Rapid Commun Mass Spectrom. 2012; 26(17):2021-6. DOI: 10.1002/rcm.6311. View

Smith D, Blakney G, Beu S, Anderson L, Weisbrod C, Hendrickson C . Ultrahigh Resolution Ion Isolation by Stored Waveform Inverse Fourier Transform 21 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. Anal Chem. 2020; 92(4):3213-3219. DOI: 10.1021/acs.analchem.9b04954. View

OConnor P, Little D, McLafferty F . Isotopic assignment in large-molecule mass spectra by fragmentation of a selected isotopic peak. Anal Chem. 1996; 68(3):542-5. DOI: 10.1021/ac950599z. View

N Nikolaev E, Heeren R, Popov A, Pozdneev A, Chingin K . Realistic modeling of ion cloud motion in a Fourier transform ion cyclotron resonance cell by use of a particle-in-cell approach. Rapid Commun Mass Spectrom. 2007; 21(22):3527-46. DOI: 10.1002/rcm.3234. View

N Nikolaev E, Jertz R, Grigoryev A, Baykut G . Fine structure in isotopic peak distributions measured using a dynamically harmonized Fourier transform ion cyclotron resonance cell at 7 T. Anal Chem. 2012; 84(5):2275-83. DOI: 10.1021/ac202804f. View

Tsybin Y, Witt M, Baykut G, Kjeldsen F, Hakansson P . Combined infrared multiphoton dissociation and electron capture dissociation with a hollow electron beam in Fourier transform ion cyclotron resonance mass spectrometry. Rapid Commun Mass Spectrom. 2003; 17(15):1759-68. DOI: 10.1002/rcm.1118. View

OConnor P, McLafferty F . High-resolution ion isolation with the ion cyclotron resonance capacitively coupled open cell. J Am Soc Mass Spectrom. 2013; 6(6):533-5. DOI: 10.1016/1044-0305(95)00232-3. View

10.

Glasner H, Riml C, Micura R, Breuker K . Label-free, direct localization and relative quantitation of the RNA nucleobase methylations m6A, m5C, m3U, and m5U by top-down mass spectrometry. Nucleic Acids Res. 2017; 45(13):8014-8025. PMC: 5570050. DOI: 10.1093/nar/gkx470. View

11.

Bray F, Bouclon J, Chiron L, Witt M, Delsuc M, Rolando C . Nonuniform Sampling Acquisition of Two-Dimensional Fourier Transform Ion Cyclotron Resonance Mass Spectrometry for Increased Mass Resolution of Tandem Mass Spectrometry Precursor Ions. Anal Chem. 2017; 89(17):8589-8593. DOI: 10.1021/acs.analchem.7b01850. View

12.

Delsuc M, Breuker K, van Agthoven M . Phase Correction for Absorption Mode Two-Dimensional Mass Spectrometry. Molecules. 2021; 26(11). PMC: 8199897. DOI: 10.3390/molecules26113388. View

13.

van Agthoven M, Lam Y, OConnor P, Rolando C, Delsuc M . Two-dimensional mass spectrometry: new perspectives for tandem mass spectrometry. Eur Biophys J. 2019; 48(3):213-229. PMC: 6449292. DOI: 10.1007/s00249-019-01348-5. View

14.

Ledford Jr E, Rempel D, Gross M . Space charge effects in Fourier transform mass spectrometry. Mass calibration. Anal Chem. 1984; 56(14):2744-8. DOI: 10.1021/ac00278a027. View

15.

Morgan T, Wootton C, Marzullo B, Paris J, Kerr A, Ellacott S . Characterization Across a Dispersity: Polymer Mass Spectrometry in the Second Dimension. J Am Soc Mass Spectrom. 2021; 32(8):2153-2161. DOI: 10.1021/jasms.1c00106. View

16.

Aizikov K, OConnor P . Use of the filter diagonalization method in the study of space charge related frequency modulation in fourier transform ion cyclotron resonance mass spectrometry. J Am Soc Mass Spectrom. 2006; 17(6):836-843. DOI: 10.1016/j.jasms.2006.02.018. View

17.

Snyder D, Szalwinski L, St John Z, Cooks R . Two-Dimensional Tandem Mass Spectrometry in a Single Scan on a Linear Quadrupole Ion Trap. Anal Chem. 2019; 91(21):13752-13762. DOI: 10.1021/acs.analchem.9b03123. View

18.

van Agthoven M, OConnor P . Two-dimensional mass spectrometry in a linear ion trap, an in silico model. Rapid Commun Mass Spectrom. 2017; 31(8):674-684. DOI: 10.1002/rcm.7836. View

19.

Halper M, Delsuc M, Breuker K, van Agthoven M . Narrowband Modulation Two-Dimensional Mass Spectrometry and Label-Free Relative Quantification of Histone Peptides. Anal Chem. 2020; 92(20):13945-13952. PMC: 7581016. DOI: 10.1021/acs.analchem.0c02843. View

20.

Floris F, van Agthoven M, Chiron L, Wootton C, Lam P, Barrow M . Bottom-Up Two-Dimensional Electron-Capture Dissociation Mass Spectrometry of Calmodulin. J Am Soc Mass Spectrom. 2017; 29(1):207-210. DOI: 10.1007/s13361-017-1812-y. View