Model Identifier
BIOMD0000001078
Short description
The model encodes the general biological process of protein synthesis and post-translational modification (PTM, such as protein phosphorylation), viewed through the eyes of a specific, widely-used experimental method. Specifically, we model measurements of pulsed stable isotope labelling of amino acids in cell culture (pSILAC), which is a method often used to quantify protein turnover (i.e. the degradation of old and replacement with new) of proteins in a cell.
Format
SBML (L2V4)
Related Publication
  • Protein-Peptide Turnover Profiling reveals the order of PTM addition and removal during protein maturation. Click here to expand
  • Henrik M Hammarén, Eva-Maria Geissen, Clement M Potel, Martin Beck, Mikhail M Savitski
  • Nature communications , 12/ 2022 , Volume 13 , Issue 1 , pages: 7431 , PubMed ID: 36460637
  • European Molecular Biology Laboratory, Genome Biology Unit, 69117, Heidelberg, Germany. henrik.hammaren@embl.de.
  • 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.
Contributors
Submitter of the first revision: Eva-Maria Geissen
Submitter of this revision: Lucian Smith
Curators: Lucian Smith, Krishna Kumar Tiwari
Modellers: Eva-Maria Geissen, Krishna Kumar Tiwari

Metadata information

is (2 statements)
BioModels Database BIOMD0000001078
BioModels Database MODEL2212160002

isDescribedBy (3 statements)
hasTaxon (1 statement)
Taxonomy Homo sapiens

hasProperty (2 statements)
Gene Ontology protein modification process
Mathematical Modelling Ontology differential equation model

unknownQualifier (1 statement)
Mathematical Modelling Ontology differential equation model

Curation status
Curated
Modelling approach(es)
differential equation model

Connected external resources

Visualisation of this model on Menelmacar platform