生物大分子结构与功能-武汉大学基础医学院.PDFVIP

生物大分子结构与功能 The ubiquitin ligase 张作鹏 2013203010020 The ubiquitin ligase Introduction Ubiquitination is a complex multistage system , mainly includes ubiquitin-activating enzyme E1, ubiquitin-carrier enzyme E2 and ubiquitin-ligase E3.In the human genome, only one gene encoding E1, less than 60 genes encoding E2s, and more than 400 genes encoding E3s.During most of ubiquitination, the substrate recognition and ubiquitin linkage is achieved by specific E3 which thought to be the key enzyme in the process of ubiquitination . Although there is a great variety of ubiquitin ligases, all of them contain some conservative structure domains to interact with ubiquitin-carrier enzyme E2. According to the diversity of the interacting domains, ubiquitin ligases can be divided into three categories ：HECT, RING-FINGER and U-BOX. Here we take some typical E3 ligases as examples to simply describe the structure, function and regulation of ubiquitin ligase. The structure of ubiquitin ligase All three categories of their unique and conservative domain of E3 ligases play a role in combination with E2s (directly or indirectly), indicates the E2s preference of E3s. Excepting HECT, RING and U – box， E3s also contain different domains to identify their specific substrates .Such as the binding domain of P53 on Mdm2 determines the recognition of P53[1], the BIR domain of XIAP determines the recognition of caspases[2]. There are about 50 HECT E3s in the human genome, HECT E3s are monomer enzymes and only a few has been identified their biochemical function. this