泛素连接酶的结构与功能研究进展

泛素化是体内蛋白质翻译后重要修饰之一,是蛋白质降解的信号.泛素连接酶E3是泛素化过程中的关键酶之一,介导活化的泛素从结合酶E2转移到底物,不同的泛素连接酶作用于不同的底物蛋白,决定了泛素化修饰的特异性.根据结构与功能机制的不同,可将泛素连接酶E3分为HECT (homologousto E6AP C terminus)家族和RING-finger家族,前者含有HECT结构域,可直接与泛素连接再将其传递给底物.RING-finger家族的E3发现较晚,庞大且功能复杂,是近年来研究的热点,此家族均包含相似的E2结合结构域和特异的底物结合部分,作为桥梁将活化的泛素从E2直接转移到靶蛋白,其本身并不与泛素发生作用.总结了这2种E3连接酶家族成员的三维结构及功能机制研究的最新进展.

Progress in Structural and Functional Study of Ubiquitin Ligases

Ubiquitination on target proteins is the signal of cellular protein degradation. Ubiquitin ligase E3 is one of the key enzymes in ubiquitination, it recognizes a specific substrate protein and recruits an ubiquitin conjugating enzyme E2, mediating the ubquitin transfer from the E2 to the substrate protein. Ubiquitin ligase E3 can be divided into two subfamilies according to their different structure characters and function mechanisms, the HECT (homologous to E6AP C terminus) family and the RING-finger family. Members of the HECT E3 share the common HECT catalytic domain, which can bind to an E2 and load the ubiquitin on themselves before catalyzing the transfer of ubiquitin to the target proteins. While the RING-finger E3 all contain an similar E2 binding domain and a unique substrate binding part, mediating direct ubiquitin transfer from the E2 to the substrate. The most recent progresses in the stuctural and functional studies of these two E3 famlies were summarized.