Arsova Borjana, Watt Michelle, Usadel Björn
Institut für Bio- und Geowissenschaften, IBG-2-Plant Sciences, Forschungszentrum Jülich, Jülich, Germany.
IBMG: Institute for Biology I, RWTH Aachen University, Aachen, Germany.
Front Plant Sci. 2018 Aug 17;9:1168. doi: 10.3389/fpls.2018.01168. eCollection 2018.
Protein post-translational modifications (PTMs) are among the fastest and earliest of plant responses to changes in the environment, making the mechanisms and dynamics of PTMs an important area of plant science. One of the most studied PTMs is protein phosphorylation. This review summarizes the use of targeted proteomics for the elucidation of the biological functioning of plant PTMs, and focuses primarily on phosphorylation. Since phosphorylated peptides have a low abundance, usually complex enrichment protocols are required for their research. Initial identification is usually performed with discovery phosphoproteomics, using high sensitivity mass spectrometers, where as many phosphopeptides are measured as possible. Once a PTM site is identified, biological characterization can be addressed with targeted proteomics. In targeted proteomics, Selected/Multiple Reaction Monitoring (S/MRM) is traditionally coupled to simple, standard protein digestion protocols, often omitting the enrichment step, and relying on triple-quadruple mass spectrometer. The use of synthetic peptides as internal standards allows accurate identification, avoiding cross-reactivity typical for some antibody based approaches. Importantly, internal standards allow absolute peptide quantitation, reported down to 0.1 femtomoles, also useful for determination of phospho-site occupancy. S/MRM is advantageous in situations where monitoring and diagnostics of peptide PTM status is needed for many samples, as it has faster sample processing times, higher throughput than other approaches, and excellent quantitation and reproducibility. Furthermore, the number of publicly available data-bases with plant PTM discovery data is growing, facilitating selection of modified peptides and design of targeted proteomics workflows. Recent instrument developments result in faster scanning times, inclusion of ion-trap instruments leading to parallel reaction monitoring- which further facilitates S/MRM experimental design. Finally, recent combination of data independent and data dependent spectra acquisition means that in addition to anticipated targeted data, spectra can now be queried for unanticipated information. The potential for future applications in plant biology is outlined.
蛋白质翻译后修饰(PTMs)是植物对环境变化做出的最快且最早的反应之一,这使得PTMs的机制和动态变化成为植物科学的一个重要领域。研究最多的PTMs之一是蛋白质磷酸化。本综述总结了靶向蛋白质组学在阐明植物PTMs生物学功能方面的应用,并主要聚焦于磷酸化。由于磷酸化肽丰度较低,通常需要复杂的富集方案来进行研究。最初的鉴定通常使用发现型磷酸蛋白质组学,借助高灵敏度质谱仪,尽可能多地测量磷酸肽。一旦确定了一个PTM位点,就可以通过靶向蛋白质组学进行生物学特性分析。在靶向蛋白质组学中,传统上选择反应监测/多反应监测(S/MRM)与简单的标准蛋白质消化方案相结合,通常省略富集步骤,并依赖于三重四极杆质谱仪。使用合成肽作为内标可以实现准确鉴定,避免了一些基于抗体方法中典型的交叉反应。重要的是,内标可以实现绝对肽定量,低至0.1飞摩尔,这对于确定磷酸化位点占有率也很有用。当需要对许多样品的肽PTM状态进行监测和诊断时,S/MRM具有优势,因为它具有更快的样品处理时间、比其他方法更高的通量以及出色的定量和重现性。此外,拥有植物PTM发现数据的公开数据库数量正在增加,这有助于选择修饰肽和设计靶向蛋白质组学工作流程。最近的仪器发展导致扫描时间更快,离子阱仪器的加入带来了平行反应监测,这进一步促进了S/MRM实验设计。最后,最近数据独立和数据依赖光谱采集的结合意味着除了预期的靶向数据外,现在还可以查询光谱以获取意外信息。本文还概述了其在植物生物学未来应用的潜力。