Proteomics Program, the Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
Proteomics Program, the Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
Trends Biochem Sci. 2019 Nov;44(11):943-960. doi: 10.1016/j.tibs.2019.06.003. Epub 2019 Jul 8.
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.
蛋白质被多种翻译后修饰（PTMs）所修饰，这些修饰调节蛋白质的时空功能。最近基于质谱（MS）的研究已经在哺乳动物蛋白质组中鉴定了数十万种 PTM 位点。然而，调节单个位点的信号线索和酶通常是未知的，它们的功能作用也尚未被阐明。PTM 位点化学计量的定量可以帮助优先考虑功能分析的位点，并且对于构建 PTM 依赖性蛋白质调节的机制模型很重要。在这里，我们回顾了 PTM 位点化学计量的概念，批判性地评估了用于定量 PTM 位点化学计量的不同基于 MS 的方法的优点和缺点，并讨论了化学计量在告知修饰位点的生物学功能方面的有用性和局限性。
