利用核磁共振法探讨类泛素媒介的信息传导分子机制（英文）

Probing the Molecular Basis of SUMO-Mediated Signaling Pathway by NMR

转译后类泛素修饰调控多项细胞活动,此信息传导的途径为:第一步将类泛素(SUMO)接于E1活化蛋白,第二步将SUMO转移到E2共轭蛋白(Ubc9),然后帮助受体蛋白完成类泛素化,最后借由蛋白酶去除类泛素完成整个传导过程.受体蛋白的类泛素化调控基本上靠Ubc9来辨识受体蛋白上的特殊类泛素序列(SM),在某些情况下亦可借由E3辨识完成.而类泛素辨识序列功效的发挥则依赖于招慕含有类泛素辨识序列(SIM)的感应蛋白来实现.此外原核细胞的类泛素化皆有形成多聚类泛素(poly-SUMO)化的能力.多聚类泛素化修饰可被含多聚类泛素辨识序列(poly-SIM)的蛋白质如RNF4识别,促进受体蛋白的多聚类泛素化,并导致目标蛋白的分解.该文综述了作者所在研究组近年来利用核磁共振法研究类泛素介导的信息传导分子机制方面的成果.

Post-translational modification by Small Ubiquitin-like MOdifier （SUMO） proteins regulates a diverse array of cellular events. The signaling process is initiated by attaching SUMO to the E1 activating protein. In the second step SUMO is transferred to E2 conjugating protein （Ubc9）. Lastly, Ubc9 couples SUMO to a target substrate covalently. The process is terminated by protease removal of SUMOs from the substrates. Sumoylation is regulated primarily through specific recognition of the sumoylation motif （SM） by Ubc9 and, in some cases, by E3-substrate recognition. The functional consequences of SUMO modification are mostly mediated by recruitment of effector proteins that contain a SUMO Interaction Motif （SIM）. Furthermore, SUMO can form poly-SUMO conjugate, which can be recognized by proteins containing poly-SIMs, such as the RING-finger 4 （RNF4） ubiquitin E3 ligase. RNF4 contains four SIMs that facilitate poly-SUMO-specific ubiquitination and targets poly-sumoylated proteins for degradation. Here we review NMR structure-functional studies, conducted in our laboratory and aimed at dissecting the molecular basis of SUMO-mediated pathway.