Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complex
Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complex
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DOI：
10.1038/35042620
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发表时间：
2000-11-16
期刊：
影响因子：
64.8
通讯作者：
Pavietich, NP
中科院分区：
文献类型：
--
作者：
Schulman, BA;Carrano, AC;Pavietich, NP
F-box蛋白是一个大家族的成员，它通过靶向蛋白（如细胞周期蛋白、细胞周期蛋白依赖性激酶抑制剂、I κ b α和β -catenin）进行泛素化来调节细胞周期、免疫反应、信号级联和发育程序（参见文献1-3）。F-box蛋白是SCF （Skp1-Cullin-F-box蛋白）泛素-蛋白连接酶的底物识别组分（4,5）。它们通过与Skp1相互作用的F-box基序结合SCF恒定催化核心，并通过其可变的蛋白质-蛋白质相互作用结构域结合底物(6)。大量的F-box蛋白被认为允许许多不同底物的泛素化(6)。大多数生物体都有几个Skp1家族成员，但这些Skp1同源物的功能以及不同F-box和Skp1蛋白之间的识别规则仍然未知。这里我们描述了与Skp1结合的人类F-box蛋白Skp2的晶体结构。Skp1通过涉及F-box和底物识别结构域的两部分界面招募F-box蛋白。该结构提出了不同Skp1家族成员进化成不同的F-box蛋白亚群的可能性，并表明F-box蛋白不仅可以招募底物，还可以将其定位在泛素化反应的最佳位置。
F-box proteins are members of a large family that regulates the cell cycle, the immune response, signalling cascades and developmental programmes by targeting proteins, such as cyclins, cyclin-dependent kinase inhibitors, I kappaB alpha and beta -catenin, for ubiquitination (reviewed in refs 1-3). F-box proteins are the substrate-recognition components of SCF (Skp1-Cullin-F-box protein) ubiquitin-protein ligases(4,5). They bind the SCF constant catalytic core by means of the F-box motif interacting with Skp1, and they bind substrates through their variable protein-protein interaction domains(6). The large number of F-box proteins is thought to allow ubiquitination of numerous, diverse substrates(6). Most organisms have several Skp1 family members, but the function of these Skp1 homologues and the rules of recognition between different F-box and Skp1 proteins remain unknown. Here we describe the crystal structure of the human F-box protein Skp2 bound to Skp1. Skp1 recruits the F-box protein through a bipartite interface involving both the F-box and the substrate-recognition domain. The structure raises the possibility that different Skp1 family members evolved to function with different subsets of F-box proteins, and suggests that the F-box protein may not only recruit substrate, but may also position it optimally for the ubiquitination reaction.