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

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

SUBMITTER: Hammaren HM 

PROVIDER: S-EPMC9718778 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature