Combinatorial degradomics: Precision tools to unveil proteolytic processes in biological systems.
Combinatorial degradomics: Precision tools to unveil proteolytic processes in biological systems.
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DOI：
10.1016/j.bbapap.2020.140392
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发表时间：
2020-02
期刊：
影响因子：
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通讯作者：
Simonas Savickas;Philipp Kastl;U. A. D. Keller
中科院分区：
文献类型：
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作者：
Simonas Savickas;Philipp Kastl;U. A. D. Keller
蛋白质的生物活性在许多水平上受到调控，从转录和翻译的控制到翻译后修饰（PTM）。蛋白质水解过程是一种不可逆的PTM，产生一种成熟蛋白质的新异构体，称为蛋白质形态。蛋白质形态动力学是当前蛋白质组学研究的一个主要焦点，因为它与许多病理状况有关。基于质谱（MS）的蛋白质组学和ptm特异性富集工作流程已成为研究体外和体内蛋白质形成的首选方法。在这里，我们概述了目前可用的基于质谱的降解组学方法，并概述了如何将它们最佳地应用于蛋白酶裂解事件的研究。我们讨论了所选方法的优点和缺点，并描述了降解组学技术的最新进展。通过引入组合降解组学的概念，结合了全球发现降解组学和高度敏感的靶向降解组学，我们展示了基于ms的降解组学如何进一步发展成为生物医学蛋白酶研究的有力工具。
The biological activity of a protein is regulated at many levels ranging from control of transcription and translation to post-translational modifications (PTM). Proteolytic processing is an irreversible PTM generating novel isoforms of a mature protein termed proteoforms. Proteoform dynamics is a major focus of current proteome research, since it has been associated with many pathological conditions. Mass-spectrometry (MS)-based proteomics and PTM-specific enrichment workflows have become the methods of choice to study proteoformsin vitroandin vivo. Here, we give an overview of currently available MS-based degradomics methods and outline how they can be optimally applied to study protease cleavage events. We discuss the advantages and disadvantages of selected approaches and describe state-of-the-art improvements in degradomics technologies. By introducing the concept of combinatorial degradomics, a combination of global discovery degradomics and highly sensitive targeted degradomics, we demonstrate how MS-based degradomics further evolves as a powerful tool in biomedical protease research.