Mass spectrometry-based detection and assignment of protein posttranslational modifications.

Mass spectrometry-based detection and assignment of protein posttranslational modifications.
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DOI:
10.1021/cb500904b
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发表时间:
2015-01-16
影响因子:
4
通讯作者:
Burlingame, Alma L.
Burlingame, Alma L.
中科院分区:
生物学2区
文献类型:
--
作者:
Doll, Sophia;Burlingame, Alma L.

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基于质谱(MS)的蛋白质组学的最新进展允许在单个实验中鉴定和定量数千个翻译后修饰(PTM)位点。这是由于开发了更有效的课堂丰富策略、新的高性能仪器和具有严格评分策略的生物信息学算法。更广泛地使用这些组合的能力,导致了我们的知识的复杂性的PTM介导的生物过程的巨大扩展。最活跃的类别包括磷酸化、泛素化、O-GlcNAc化、甲基化和乙酰化。最近出现了琥珀酰化、SUMO酰化和瓜氨酸化。迄今为止,在人类蛋白质组中已确定的约260 000个PTM位点中,只有少数被分配到关键的调控和/或其他生物学作用。在这里,我们提供了一个更新的MS为基础的PTM分析,重点是当前的富集策略加上革命性的进展,在高性能MS。此外,我们讨论的例子,最近描述的生物作用的PTM的发现和解决的挑战,定义特定位点的功能。
Recent advances in mass spectrometry (MS)-based proteomics allow the identification and quantitation of thousands of posttranslational modification (PTM) sites in a single experiment. This follows from the development of more effective class enrichment strategies, new high performance instrumentation and bioinformatic algorithms with rigorous scoring strategies. More widespread use of these combined capabilities have led to a vast expansion in our knowledge of the complexity of biological processes mediated by PTMs. The classes most actively pursued include phosphorylation, ubiquitination, O-GlcNAcylation, methylation, and acetylation. Very recently succinylation, SUMOylation, and citrullination have emerged. Among the some 260 000 PTM sites that have been identified in the human proteome thus far, only a few have been assigned to key regulatory and/or other biological roles. Here, we provide an update of MS-based PTM analyses, with a focus on current enrichment strategies coupled with revolutionary advances in high performance MS. Furthermore, we discuss examples of the discovery of recently described biological roles of PTMs and address the challenges of defining site-specific functions.
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