Status of Large-scale Analysis of Post-translational Modifications by Mass Spectrometry

Abstract

Cellular function can be controlled through the gene expression program, but often protein post-translational modifications (PTMs) provide a more precise and elegant mechanism. Key functional roles of specific modification events--for instance, during the cell cycle--have been known for decades, but only in the past 10 years has mass-spectrometry-(MS)-based proteomics begun to reveal the true extent of the PTM universe. In this overview for the special PTM issue of Molecular and Cellular Proteomics, we take stock of where MS-based proteomics stands in the large-scale analysis of protein modifications. For many PTMs, including phosphorylation, ubiquitination, glycosylation, and acetylation, tens of thousands of sites can now be confidently identified and localized in the sequence of the protein. The quantification of PTM levels between different cellular states is likewise established, with label-free methods showing particular promise. It is also becoming possible to determine the absolute occupancy or stoichiometry of PTM sites on a large scale. Powerful software for the bioinformatic analysis of thousands of PTM sites has been developed. However, a complete inventory of sites has not been established for any PTM, and this situation will persist into the foreseeable future. Furthermore, although PTM coverage by MS-based methods is impressive, it still needs to be improved, especially in tissues and in clinically relevant systems. The central challenge for the field is to develop streamlined methods for determining biological functions for the myriad of modifications now known to exist.

Cited by papers we hold 14

• Automated single-cell proteomics providing sufficient proteome depth to study complex biology beyond cell type classifications · 2024
  No notice
• Rapid and In-Depth Coverage of the (Phospho-)Proteome With Deep Libraries and Optimal Window Design for dia-PASEF · 2022
  No notice
• Bacterial Sirtuins Overview: An Open Niche to Explore · 2021
  Not checked
• Origin of the Phosphoprotein Phosphatase (PPP) sequence family in Bacteria: Critical ancestral sequence changes, radiation patterns and substrate binding features · 2021
  Not checked
• Rapid and site-specific deep phosphoproteome profiling by data-independent acquisition without the need for spectral libraries · 2020
  No notice
• Inferring the molecular and phenotypic impact of amino acid variants with MutPred2 · 2020
  No notice
• Microcins in Enterobacteriaceae: Peptide Antimicrobials in the Eco-Active Intestinal Chemosphere · 2019
  No notice
• Nuclear Signaling of Plant MAPKs · 2018
  No notice
• An Optimized Shotgun Strategy for the Rapid Generation of Comprehensive Human Proteomes · 2017
  No notice
• Global mapping of CARM1 substrates defines enzyme specificity and substrate recognition · 2017
  No notice
• Proteomic Stable Isotope Probing Reveals Biosynthesis Dynamics of Slow Growing Methane Based Microbial Communities · 2016
  Not checked
• Proteome-wide identification of the endogenous ADP-ribosylome of mammalian cells and tissue · 2016
  No notice
• Ubiquitin modifications · 2016
  No notice
• Making proteomics data accessible and reusable: Current state of proteomics databases and repositories · 2015
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.