ROSics: chemistry and proteomics of cysteine modifications in redox biology.

ROSics: chemistry and proteomics of cysteine modifications in redox biology.
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DOI:
10.1002/mas.21430
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发表时间:
2015-03
影响因子:
6.6
通讯作者:
Lee, Kong-Joo
Lee, Kong-Joo
中科院分区:
化学2区
文献类型:
--
作者:
Kim, Hee-Jung;Ha, Sura;Lee, Hee Yoon;Lee, Kong-Joo

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蛋白质中的翻译后修饰(PTM)决定了它们的功能和调节。蛋白质组学工具可用于鉴定PTM,事实证明,这些工具对于扩大这些掌握着生物过程关键的自然工具的清单是非常宝贵的。半胱氨酸(Cysteine,Cys)是氨基酸残基中含量最少(1-2%)的一种,在维持蛋白质结构稳定、参与酶活性部位、调节蛋白质功能和与金属结合等方面发挥着关键作用。Cys残基是活性氧物种(ROS)的主要靶标,ROS是各种生物过程的重要介体和调节物。因此,有必要确定含有半胱氨酸的ROS靶蛋白,以及它们的PTM的位置和种类。帮助鉴定活性半胱氨酸残基上的PTM的尖端蛋白质组学工具也揭示了半胱氨酸残基以多种方式被修饰。这些修饰包括二硫化物、硫代亚磺酸和硫代磺酸的形成,氧化为亚磺酸、亚磺酸、磺酸和硫磺酸,转化为脱氢丙氨酸(DHA)和丝氨酸,棕榈酰化和法尼化,与谷胱甘肽、4-羟基壬烯醛和15-脱氧PGJ2形成化学加合物,以及各种其他化学物质。我们综述了相关的ROS生物学,半胱氨酸残基的可能化学反应,以及用于快速、有效和灵敏地鉴定涉及氧化还原敏感蛋白反应性半胱氨酸残基的各种新的PTM的蛋白质组学策略。我们建议给这门在分子水平上描述ROS作用方式原理的科学起一个新的名字,ROSICS。©2014作者。由威利期刊出版公司出版的质谱学评论。质量规范修订版34:184-208,2015。
Post-translational modifications (PTMs) occurring in proteins determine their functions and regulations. Proteomic tools are available to identify PTMs and have proved invaluable to expanding the inventory of these tools of nature that hold the keys to biological processes. Cysteine (Cys), the least abundant (1–2%) of amino acid residues, are unique in that they play key roles in maintaining stability of protein structure, participating in active sites of enzymes, regulating protein function and binding to metals, among others. Cys residues are major targets of reactive oxygen species (ROS), which are important mediators and modulators of various biological processes. It is therefore necessary to identify the Cys-containing ROS target proteins, as well as the sites and species of their PTMs. Cutting edge proteomic tools which have helped identify the PTMs at reactive Cys residues, have also revealed that Cys residues are modified in numerous ways. These modifications include formation of disulfide, thiosulfinate and thiosulfonate, oxidation to sulfenic, sulfinic, sulfonic acids and thiosulfonic acid, transformation to dehydroalanine (DHA) and serine, palmitoylation and farnesylation, formation of chemical adducts with glutathione, 4-hydroxynonenal and 15-deoxy PGJ2, and various other chemicals. We present here, a review of relevant ROS biology, possible chemical reactions of Cys residues and details of the proteomic strategies employed for rapid, efficient and sensitive identification of diverse and novel PTMs involving reactive Cys residues of redox-sensitive proteins. We propose a new name, “ROSics,” for the science which describes the principles of mode of action of ROS at molecular levels. © 2014 The Authors. Mass Spectrometry Reviews Published by Wiley Periodicals, Inc. Rapid Commun. Mass Spec Rev 34:184–208, 2015.
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