Structural basis of intersubunit recognition in elongin BC-cullin 5-SOCS box ubiquitin-protein ligase complexes
Structural basis of intersubunit recognition in elongin BC-cullin 5-SOCS box ubiquitin-protein ligase complexes
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DOI：
10.1107/s0907444913011220
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发表时间：
2013-08-01
期刊：
影响因子：
--
通讯作者：
Oh, Byung-Ha
中科院分区：
文献类型：
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作者：
Kim, Young Kwan;Kwak, Mi-Jeong;Oh, Byung-Ha
cullin-RING遍在蛋白连接酶是多亚基复合物，可遍在多种蛋白质。由人类基因组编码的六种不同的cullin选择性地与不同的衔接子和底物受体配对。目前尚不清楚cullin-2（Cul 2）和cullin-5（Cul 5）如何特异性地与它们的衔接子延伸蛋白BC和含有SOCS盒的底物受体结合。在这里，晶体学和突变分析的四元复合物之间的N-末端一半的Cul 5，延伸蛋白BC和SOCS 2的报告。Cul 5通过在Cul 2中高度保守但在其他cullin中不高度保守的残基与延伸蛋白BC广泛相互作用。Cul 5也与SOCS 2相互作用，但仅通过两个残基，Pro 184和Arg 186，它们位于SOCS盒的C-末端部分，称为Cul 5盒。Pro 184与Cul 5的Trp 53发生环-环相互作用，Cul 5的Trp 53在Cul 2中被丙氨酸取代。这种相互作用显示出显著地有助于Cul 5和SOCS 2-延伸蛋白BC之间的总体结合亲和力。这项研究提供了潜在的Cul 5和Cul 2的特异性的延伸蛋白BC和他们的优先协会Cul 5或Cul 2盒含有底物受体的结构基础。
The cullin-RING ubiquitin ligases are multisubunit complexes that ubiquitinate various proteins. Six different cullins encoded by the human genome selectively pair with different adaptors and substrate receptors. It is presently poorly understood how cullin-2 (Cul2) and cullin-5 (Cul5) associate specifically with their adaptor elongin BC and a SOCS-box-containing substrate receptor. Here, crystallographic and mutational analyses of a quaternary complex between the N-terminal half of Cul5, elongin BC and SOCS2 are reported. Cul5 interacts extensively with elongin BC via residues that are highly conserved in Cul2 but not in other cullins. Cul5 also interacts with SOCS2, but via only two residues, Pro184 and Arg186, which are located in the C-terminal part of the SOCS box called the Cul5 box. Pro184 makes a ring-to-ring interaction with Trp53 of Cul5, which is substituted by alanine in Cul2. This interaction is shown to contribute significantly to the overall binding affinity between Cul5 and SOCS2-elongin BC. This study provides structural bases underlying the specificity of Cul5 and Cul2 for elongin BC and their preferential association with Cul5 or Cul2 box-containing substrate receptors.