Proteome dynamics from heavy water metabolic labeling and peptide tandem mass spectrometry

Ahmad Borzou, Vugar R. Sadygov, William Zhang, Rovshan Sadygov

Research output: Contribution to journalArticle

Abstract

Protein homeostasis (proteostasis) is a result of a dynamic equilibrium between protein synthesis and degradation. It is important for healthy cell/organ functioning and is often associated with diseases such as neurodegenerative diseases and non-Alcoholic Fatty Liver disease. Heavy water metabolic labeling, combined with liquid-chromatography and mass spectrometry (LC-MS), is a powerful approach to study proteostasis in vivo in high throughput. Traditionally, intact peptide signals are used to estimate stable isotope incorporation in time-course experiments. The time-course of label incorporation is used to extract protein decay rate constant (DRC). Intact peptide signals, computed from integration in chromatographic time and mass-to-charge ratio (m/z) domains, usually, provide an accurate estimate of label incorporation. However, sample complexity (co-elution), limited dynamic range, and low signal-to-noise ratio (S/N) may adversely interfere with the peptide signals. These artifacts complicate the DRC estimations by distorting peak shape in chromatographic time and m/z domains. Fragment ions, on the other hand, are less prone to these artifacts and are potentially well suited in aiding DRC estimations. Here, we show that the label incorporation encoded into the isotope distributions of fragment ions reflect the isotope enrichment during the metabolic labeling with heavy water. We explore the label incorporation statistics for devising practical approaches for DRC estimations.

Original languageEnglish (US)
Article number116194
JournalInternational Journal of Mass Spectrometry
Volume445
DOIs
StatePublished - Nov 1 2019

Fingerprint

proteome
Deuterium Oxide
Heavy water
heavy water
Proteome
Labeling
Peptides
marking
decay rates
peptides
Mass spectrometry
Labels
Rate constants
mass spectroscopy
Protein Sorting Signals
Isotopes
Proteins
homeostasis
isotopes
proteins

Keywords

  • Fragment ion quantification from deuterium labeled peptides
  • Heavy water metabolic labeling
  • In vivo protein turnover
  • Protein half-life

ASJC Scopus subject areas

  • Instrumentation
  • Condensed Matter Physics
  • Spectroscopy
  • Physical and Theoretical Chemistry

Cite this

Proteome dynamics from heavy water metabolic labeling and peptide tandem mass spectrometry. / Borzou, Ahmad; Sadygov, Vugar R.; Zhang, William; Sadygov, Rovshan.

In: International Journal of Mass Spectrometry, Vol. 445, 116194, 01.11.2019.

Research output: Contribution to journalArticle

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