Department of Biochemistry, University of Toronto, 1 Kings College Circle, Toronto, Ontario M5S 1A8, Canada.
Structure. 2012 Jul 3;20(7):1141-53. doi: 10.1016/j.str.2012.04.009. Epub 2012 May 24.
The E3 ligases recruit substrate proteins for targeted ubiquitylation. Recent insights into the mechanisms of ubiquitylation demonstrate that E3 ligases can possess active regulatory properties beyond those of a simple assembly scaffold. Here, we describe the dimeric structure of the E3 ligase adaptor protein SPOP (speckle-type POZ protein) in complex with the N-terminal domain of Cul3 at 2.4 Å resolution. We find that SPOP forms large oligomers that can form heteromeric species with the closely related paralog SPOPL. In combination, SPOP and SPOPL (SPOP-like) form a molecular rheostat that can fine-tune E3 ubiquitin ligase activity by affecting the oligomeric state of the E3 complex. We propose that adaptor protein self-assembly provides a graded level of regulation of the SPOP/Cul3 E3 ligase toward its multiple protein substrates.
E3 连接酶招募底物蛋白进行靶向泛素化。最近对泛素化机制的深入了解表明，E3 连接酶除了具有简单的组装支架外，还可以具有主动的调节特性。在这里，我们描述了 E3 连接酶接头蛋白 SPOP（斑状 POZ 蛋白）与 Cul3 的 N 端结构域在 2.4 Å 分辨率下的二聚体结构。我们发现 SPOP 形成大的寡聚体，这些寡聚体可以与密切相关的同源物 SPOPL 形成异源物种。SPOP 和 SPOPL（SPOP 样）共同形成分子变阻器，通过影响 E3 复合物的寡聚状态，可以精细调节 E3 泛素连接酶的活性。我们提出，接头蛋白的自组装为 SPOP/Cul3 E3 连接酶对其多种蛋白质底物提供了一个分级的调节水平。
