Linking post-translational modifications and protein turnover by site-resolved protein turnover profiling

Jana Zecha, Wassim Gabriel, Ria Spallek, Yun-Chien Chang, Julia Mergner, Mathias Wilhelm, Florian Bassermann, Bernhard Kuster (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)
5 Downloads (Pure)

Abstract

Proteome-wide measurements of protein turnover have largely ignored the impact of post-translational modifications (PTMs). To address this gap, we employ stable isotope labeling and mass spectrometry to measure the turnover of >120,000 peptidoforms including >33,000 phosphorylated, acetylated, and ubiquitinated peptides for >9,000 native proteins. This site-resolved protein turnover (SPOT) profiling discloses global and site-specific differences in turnover associated with the presence or absence of PTMs. While causal relationships may not always be immediately apparent, we speculate that PTMs with diverging turnover may distinguish states of differential protein stability, structure, localization, enzymatic activity, or protein-protein interactions. We show examples of how the turnover data may give insights into unknown functions of PTMs and provide a freely accessible online tool that allows interrogation and visualisation of all turnover data. The SPOT methodology is applicable to many cell types and modifications, offering the potential to prioritize PTMs for future functional investigations.

Original languageEnglish
Article number165
Number of pages14
JournalNature Communications
Volume13
DOIs
Publication statusPublished - 10 Jan 2022

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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