a Unit of Proteomics , Centro Cardiologico Monzino IRCCS , Milan , Italy.
Expert Rev Proteomics. 2018 Jun;15(6):477-502. doi: 10.1080/14789450.2018.1484283.
Post-translational modifications (PTMs) have an important role in the regulation of protein function, localization, and interaction with other molecules. PTMs apply a dynamic control of proteins in both physiological and pathological conditions. The study of disease-specific PTMs allows identifying potential biomarkers and developing effective drugs. Enrichment techniques combined with high-resolution mass spectrometry (MS)/MS analysis provide attractive results on PTM characterization. Selected reaction monitoring/multiple reaction monitoring (SRM/MRM) is a powerful targeted assay for the quantitation and validation of PTMs in complex biological samples. Areas covered: The most frequent PTMs are described in terms of biological role and analytical methods commonly used to detect them. The applications of SRM/MRM for the absolute quantitation of PTMs are reported, and a specific section is focused on PTM detection in proteins that are involved in the cardiovascular system and heart diseases. Expert commentary: PTM characterization in relation to disease pathology is still in progress, but targeted proteomics by LC-MS/MS has significantly upgraded our knowledge in the last few years. Advances in enrichment strategies and software tools will facilitate the interpretation of high PTM complexity. Promising studies confirm the great potential of SRM/MRM to study PTMs in the cardiovascular field, and PTMomics could be very useful in the clinical perspective.
翻译后修饰(PTMs)在蛋白质功能、定位以及与其他分子的相互作用调控中发挥着重要作用。PTMs在生理和病理条件下对蛋白质进行动态调控。对疾病特异性PTMs的研究有助于识别潜在的生物标志物并开发有效的药物。富集技术与高分辨率质谱(MS)/串联质谱(MS)分析相结合,在PTM表征方面取得了引人注目的成果。选择反应监测/多反应监测(SRM/MRM)是一种强大的靶向分析方法,用于复杂生物样品中PTMs的定量和验证。涵盖领域:从生物学作用和常用于检测它们的分析方法方面描述了最常见的PTMs。报道了SRM/MRM在PTMs绝对定量中的应用,并且有一个特定部分聚焦于参与心血管系统和心脏病的蛋白质中的PTM检测。专家评论:与疾病病理学相关的PTM表征仍在进行中,但液相色谱-串联质谱(LC-MS/MS)靶向蛋白质组学在过去几年中显著提升了我们的认知。富集策略和软件工具的进步将有助于解读高度复杂的PTMs。有前景的研究证实了SRM/MRM在心血管领域研究PTMs的巨大潜力,并且从临床角度来看,PTM组学可能非常有用。