泛素链的形成机理  

Mechanisms of Ubiquitin Chain Formation

作　　者：王亚楠 赵博[1] WANG Ya-Nan;ZHAO Bo(Engineering Research Center of Cell and Therapeutic Antibody Ministry of Education,School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240,China)

机构地区：[1]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

出　　处：《生物化学与生物物理进展》2021年第5期515-528,共14页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(31770921,31971187)资助项目。

摘　　要：泛素化是真核细胞中重要的蛋白质翻译后修饰过程,通过靶向蛋白质降解或其他信号途径参与多种细胞功能.底物蛋白的多聚泛素化修饰是一个持续的过程,其中不仅涉及复杂泛素系统相关酶的参与,而且存在更为复杂的结构上相互作用与泛素链组装机理.不同的泛素链修饰决定了底物蛋白下游的不同命运,泛素结合酶E2在泛素链形成中的重要作用受到越来越多的关注.对泛素链形成机理的深入研究与认识有利于发现与泛素系统相关的疾病靶点和利用泛素化调控方法进行治疗.本综述总结了E2和E3如何决定不同泛素链形成的机制和相关的结构信息,以及两种不同的泛素链组装机制.Ubiquitination is an important protein post-translational modification process in eukaryotic cells,participating in a variety of cellular functions such as protein degradation and signaling pathways.The polyubiquitination modification of the substrate proteins is a continuous process,which not only involves the complex participation of enzymes related to ubiquitin system,but also refers to more complex structural interactions and ubiquitin chain assembly mechanisms.Ubiquitin chain modifications determine the fate of the downstream substrate proteins.The crucial role of ubiquitin-conjugating enzyme E2 in the formation of ubiquitin chains has attracted more and more attentions.Understanding of the mechanisms of ubiquitin chain formation is conducive to the discovery of disease targets and treatment related to the ubiquitin system.In this review,we summarize the research progress of the mechanisms of ubiquitin chain formation,involving how E2 reacting with different types of E3 determine the type and the assembly process of ubiquitin chain formed on the substrates,with complex structural information provided.Two different mechanisms on how ubiquitin chain assembly,including the sequential addition mechanism and the en bloc transfer mechanism,are also discussed.

关 键 词：泛素链 泛素结合酶E2 泛素连接酶E3 泛素链特异性 泛素链组装 

分 类 号：Q51[生物学—生物化学] Q71