English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Protein-Peptide Turnover Profiling reveals the order of PTM addition and removal during protein maturation

MPS-Authors
/persons/resource/persons232071

Beck,  Martin       
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)

s41467-022-35054-2.pdf
(Any fulltext), 3MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Hammarén, H. M., Geissen, E.-M., Potel, C. M., Beck, M., & Savitski, M. M. (2022). Protein-Peptide Turnover Profiling reveals the order of PTM addition and removal during protein maturation. Nature Communications, 13: 7431. doi:10.1038/s41467-022-35054-2.


Cite as: https://hdl.handle.net/21.11116/0000-000B-B2E9-5
Abstract
Post-translational modifications (PTMs) regulate various aspects of protein function, including degradation. Mass spectrometric methods relying on pulsed metabolic labeling are popular to quantify turnover rates on a proteome-wide scale. Such data have traditionally been interpreted in the context of protein proteolytic stability. Here, we combine theoretical kinetic modeling with experimental pulsed stable isotope labeling of amino acids in cell culture (pSILAC) for the study of protein phosphorylation. We demonstrate that metabolic labeling combined with PTM-specific enrichment does not measure effects of PTMs on protein stability. Rather, it reveals the relative order of PTM addition and removal along a protein's lifetime-a fundamentally different metric. This is due to interconversion of the measured proteoform species. Using this framework, we identify temporal phosphorylation sites on cell cycle-specific factors and protein complex assembly intermediates. Our results thus allow tying PTMs to the age of the modified proteins.