Analysis and Interpretation of Protein Post-Translational Modification Site Stoichiometry

TY - JOUR

T1 - Analysis and Interpretation of Protein Post-Translational Modification Site Stoichiometry

AU - Prus, Gabriela

AU - Hoegl, Annabelle

AU - Weinert, Brian T

AU - Choudhary, Chunaram

PY - 2019/11

Y1 - 2019/11

N2 - Proteins are decorated with a diverse array of post-translational modifications (PTMs) that regulate their spatial and temporal functions. Recent mass spectrometry (MS)-based studies have identified hundreds of thousands of PTM sites in mammalian proteomes. However, the signaling cues and enzymes regulating individual sites are often not known and their functional roles remain uncharacterized. Quantification of PTM site stoichiometry can help in prioritizing sites for functional analyses and is important for constructing mechanistic models of PTM-dependent protein regulation. Here, we review the concept of PTM site stoichiometry, critically evaluate the merits and drawbacks of different MS-based methods used for quantifying PTM site stoichiometry, and discuss the usefulness and limitations of stoichiometry in informing on the biological function of modified sites.

AB - Proteins are decorated with a diverse array of post-translational modifications (PTMs) that regulate their spatial and temporal functions. Recent mass spectrometry (MS)-based studies have identified hundreds of thousands of PTM sites in mammalian proteomes. However, the signaling cues and enzymes regulating individual sites are often not known and their functional roles remain uncharacterized. Quantification of PTM site stoichiometry can help in prioritizing sites for functional analyses and is important for constructing mechanistic models of PTM-dependent protein regulation. Here, we review the concept of PTM site stoichiometry, critically evaluate the merits and drawbacks of different MS-based methods used for quantifying PTM site stoichiometry, and discuss the usefulness and limitations of stoichiometry in informing on the biological function of modified sites.

U2 - 10.1016/j.tibs.2019.06.003

DO - 10.1016/j.tibs.2019.06.003

M3 - Review

C2 - 31296352

SN - 0968-0004

VL - 44

SP - 943

EP - 960

JO - Trends in Biochemical Sciences

JF - Trends in Biochemical Sciences

IS - 11

ER -