Department of Biotechnology and Biomedicine, Technical University of Denmark, DK-2800, Kongens Lyngby, Denmark.
Department of Biotechnology and Biomedicine, Technical University of Denmark, DK-2800, Kongens Lyngby, Denmark.
Curr Opin Chem Biol. 2021 Feb;60:89-96. doi: 10.1016/j.cbpa.2020.09.009. Epub 2020 Nov 18.
Proteome dynamics is governed by transcription, translation, and post-translational modifications. Limited proteolysis is an irreversible post-translational modification that generates multiple but unique proteoforms from almost every native protein. Elucidating these proteoforms and understanding their dynamics at a system-wide level is of utmost importance because uncontrolled proteolytic cleavages correlate with many pathologies. Mass spectrometry-based degradomics has revolutionized protease research and invented workflows for global identification of protease substrates with resolution down to precise cleavage sites. In this review, we provide an overview of current strategies in protease substrate degradomics and introduce the concept of workflow, mass spectrometry-based and in silico enrichment of protein termini with the perspective of full deconvolution of digital proteome maps for precision medicine, and degradomics biomarker diagnostics.
蛋白质组动力学受转录、翻译和翻译后修饰的控制。有限的蛋白水解是一种不可逆的翻译后修饰，它几乎可以从每种天然蛋白质中产生多种但独特的蛋白形式。阐明这些蛋白形式并在系统水平上理解它们的动态至关重要，因为不受控制的蛋白水解裂解与许多病理学有关。基于质谱的降解组学彻底改变了蛋白酶研究，并发明了用于全局鉴定蛋白酶底物的工作流程，分辨率可精确到切割位点。在这篇综述中，我们提供了蛋白酶底物降解组学的当前策略概述，并介绍了基于工作流程、基于质谱和基于计算的蛋白质末端富集的概念，以期对数字蛋白质组图谱进行精确医学和降解组学生物标志物诊断的全面剖析。
