解密泛素链的亲和工具
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上海交通大学细胞工程和抗体药物教育部工程研究中心,上海交通大学药学院,上海 200240

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国家自然科学基金(31770921)资助项目.


Affinity Tools for Decrypting The Ubiquitin Chains
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Engineering Research Center of Cell and Therapeutic Antibody Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China

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This work was supported by a grant from The National Natural Science Foundation of China (31770921).

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    摘要:

    泛素化是最具多样性的蛋白质翻译后修饰之一,广泛参与蛋白质降解、细胞信号转导、DNA损伤修复等重要的生物学过程. 其中,泛素的8个位点(M1、K6、K11、K27、K29、K33、K48、K63)都可以与另一个泛素分子的C末端结合,形成结构复杂的泛素链. 不同结构泛素链的功能不同. 由于缺乏检测泛素链的特异性工具,许多类型泛素链的功能尚未清楚. 已开发的泛素连接特异性抗体等亲和试剂为研究泛素链提供了重要的分析工具. 本文综述了目前已报道的几种泛素连接特异性抗体的开发以及应用,同时总结了其他可分析泛素链的特异性亲和工具,例如Affimer、基于UBD的荧光传感蛋白等. 同时,本文还对开发泛素连接特异性抗体所需抗原的获得方法进行了简单的介绍.

    Abstract:

    Protein ubiquitination is one of the most versatile post-translational modifications, and is widely involved in multiple cellular processes including protein degradation, cellular signaling transduction and DNA damage responses. The eight sites (M1, K6, K11, K27, K29, K33, K48, K63) of ubiquitin help to form individual complex chains by being attached to C-terminus of another ubiquitin molecule. In addition, these different ubiquitin chains play distinct biological functions. However, functions of most ubiquitin chain types are poorly understood, due to the lack of tools that enable ubiquitin linkage-specific detection. Affinity reagents such as ubiquitin linkage-specific antibodies are powerful tools for the studies of the ubiquitin chains. This review focuses on the development and applications of several ubiquitin linkage-specific antibodies, as well as other specific affinity tools, which can be used for identifying of ubiquitin chains such as Affimer and UBD-based fluorescent sensors proteins. This review also briefly introduces the methods of obtaining antigens for the discovery of these ubiquitin linkage-specific antibodies.

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李贞,赵博.解密泛素链的亲和工具[J].生物化学与生物物理进展,2019,46(9):845-857

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  • 收稿日期:2019-03-05
  • 最后修改日期:2019-08-06
  • 接受日期:2019-08-19
  • 在线发布日期: 2019-12-19
  • 出版日期: 2019-09-20