Journal of Proteomics ( IF 2.8 ) Pub Date : 2020-12-25 , DOI: 10.1016/j.jprot.2020.104089 Prashant Kaushal 1 , Cheolju Lee 2
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N-terminomics is a rapidly evolving branch of proteomics that encompasses the study of protein N-terminal sequence. A proteome-wide collection of such sequences has been widely used to understand the proteolytic cascades and in annotating the genome. Over the last two decades, various N-terminomic strategies have been developed for achieving high sensitivity, greater depth of coverage, and high-throughputness. We, in this review, cover how the field of N-terminomics has evolved to date, including discussion on various sample preparation and N-terminal peptide enrichment strategies. We also compare different N-terminomic methods and highlight their relative benefits and shortcomings in their implementation. In addition, an overview of the currently available bioinformatics tools and data analysis pipelines for the annotation of N-terminomic datasets is also included.
Significance
It has been recognized that proteins undergo several post-translational modifications (PTM), and a number of perturbed biological pathways are directly associated with modifications at the terminal sites of a protein. In this regard, N-terminomics can be applied to generate a proteome-wide landscape of mature N-terminal sequences, annotate their source of generation, and recognize their significance in the biological pathways. Besides, a system-wide study can be used to study complicated proteolytic machinery and protease cleavage patterns for potential therapeutic targets. Moreover, due to unprecedented improvements in the analytical methods and mass spectrometry instrumentation in recent times, the N-terminomic methodologies now offers an unparalleled ability to study proteoforms and their implications in clinical conditions. Such approaches can further be applied for the detection of low abundant proteoforms, annotation of non-canonical protein coding sites, identification of candidate disease biomarkers, and, last but not least, the discovery of novel drug targets.
中文翻译：
N术语-过去和最近的发展
N术语是蛋白质组学的一个快速发展的分支，涵盖了蛋白质N端序列的研究。这种序列的蛋白质组范围的集合已被广泛用于理解蛋白水解级联和注释基因组。在过去的二十年中，已开发出各种N端策略，以实现高灵敏度，更大覆盖深度和高通量。在这篇综述中，我们涵盖了迄今为止N术语组学领域的发展，包括对各种样品制备和N末端肽富集策略的讨论。我们还比较了不同的N端方法，并强调了它们的相对优点和缺点。此外，
意义
已经认识到蛋白质经历几种翻译后修饰（PTM），并且许多扰动的生物途径与蛋白质末端位点的修饰直接相关。在这方面，N术语可用于生成成熟的N末端序列的蛋白质组范围的图景，注释其产生的来源，并认识其在生物学途径中的重要性。此外，可以使用系统范围的研究来研究复杂的蛋白水解机制和蛋白酶切割模式，以寻找潜在的治疗靶标。此外，由于近来在分析方法和质谱仪器方面的空前改进，N术语方法论现在提供了无与伦比的研究蛋白形式及其在临床条件中的意义的能力。
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