The next frontier of post-translational modifications.
The next frontier of post-translational modifications.
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翻译后修饰的下一个前沿。
DOI：
10.1002/bip.22370
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发表时间：
2014
期刊：
影响因子：
2.9
通讯作者：
Martin,BrentR
中科院分区：
文献类型：
--
作者：
Martin,BrentR
翻译修饰（PTM），可能导致人类蛋白质组产生数百万个不同的功能成员。数百种独特的 PTM 已被描述，尽管由于工具和试剂的可用性，其中一些已被更彻底地理解。最常研究的 PTM 包括磷酸化、泛素化、糖基化、乙酰化、脂化、氧化和蛋白水解。这些独特的修饰可快速将蛋白质转变为不同的活性或非活性构象、改变极性或疏水性以影响定位、招募新的相互作用伙伴或靶向降解。大多数 PTM 发生在极性和带电氨基酸上，包括丝氨酸、苏氨酸、天冬酰胺、半胱氨酸、赖氨酸和精氨酸。即使经过数十年的磷酸化研究，随着新分析方法和工具的发展，我们对 PTM 动态和多样性的了解仍在不断扩大。显然，几乎所有蛋白质的激活、抑制和降解都需要 PTM。毫无疑问，翻译后调控的复杂性使得将基因组信息转化为蛋白质生物学功能的任务变得艰巨。本期发表了六篇综述，概述了在理解不同翻译后事件的多样性和调控方面取得的进展。放射性磷酸盐、乙酸盐、糖和脂质的代谢标记提供了蛋白质组中独特修饰的广度的第一个证据。后来，PTM特异性抗体大大增强了快速分析特定修饰的能力，尤其是那些具有足够抗原性的修饰。质谱技术的最新进展为许多 PTM 提供了第一个蛋白质组范围的视图。这些实验在选择性富集后变得更加灵敏，从而减少了丰富的未修饰肽。此类研究已鉴定出数以万计的磷酸化位点。 2 此类研究
translational modifications (PTMs), which likely lead to millions of different functional members of the human proteome. Hundreds of unique PTMs have been described, although some are more thoroughly understood due to the availability of tools and reagents. The most commonly studied PTMs include phosphorylation, ubiquitylation, glycosylation, acetylation, lipidation, oxidation, and proteolysis. These distinct modifications function to rapidly switch proteins to different active or inactive conformations, change polarity or hydrophobicity to affect localization, recruit new interaction partners, or target degradation. Most PTMs occur at polar and charged amino acids, including serine, threonine, asparagine, cysteine, lysine, and arginine. Even after decades of studying phosphorlyation, our knowledge of the dynamics and diversity of PTM continues to expand with the development of new analytical methods and tools. PTMs are clearly required for the activation, inhibition, and degradation of nearly all proteins. Undoubtedly, the complexity of post-translational regulation makes the task of translating genomic information to the biological function of proteins daunting. In this issue, six reviews are presented that outline progress in understanding the diversity and regulation of distinct posttranslational events.Metabolic labeling with radioactive phosphate, acetate, sugars, and lipids provided the first evidence of the breadth of unique modifications in the proteome. Later, PTM-specific antibodies greatly enhanced the ability to rapidly analyze specific modifications, especially those that are sufficiently antigenic. Recent advances in mass spectrometry have provided the first proteome-wide view many PTMs. These experiments are massively more sensitive after selective enrichment, which reduces abundant unmodified peptides. Such studies have identified tens of thousands of phosphorylation sites. 2 Such studies