Shimanovskaya Ekaterina, Viscardi Valeria, Lesigang Johannes, Lettman Molly M, Qiao Renping, Svergun Dmitri I, Round Adam, Oegema Karen, Dong Gang
Max F. Perutz Laboratories, Medical University of Vienna, 1030 Vienna, Austria.
Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Structure. 2014 Aug 5;22(8):1090-1104. doi: 10.1016/j.str.2014.05.009. Epub 2014 Jun 26.
Plk4 family kinases control centriole assembly. Plk4s target mother centrioles through an interaction between their cryptic polo box (CPB) and acidic regions in the centriolar receptors SPD-2/Cep192 and/or Asterless/Cep152. Here, we report a crystal structure for the CPB of C. elegans ZYG-1, which forms a Z-shaped dimer containing an intermolecular β sheet with an extended basic surface patch. Biochemical and in vivo analysis revealed that electrostatic interactions dock the ZYG-1 CPB basic patch onto the SPD-2-derived acidic region to promote ZYG-1 targeting and new centriole assembly. Analysis of a different crystal form of the Drosophila Plk4 (DmPlk4) CPB suggests that it also forms a Z-shaped dimer. Comparison of the ZYG-1 and DmPlk4 CPBs revealed structural changes in the ZYG-1 CPB that confer selectivity for binding SPD-2 over Asterless-derived acidic regions. Overall, our findings suggest a conserved mechanism for centriolar docking of Plk4 homologs that initiate daughter centriole assembly.
Plk4家族激酶控制中心粒组装。Plk4s通过其隐蔽的polo框（CPB）与中心粒受体SPD-2/Cep192和/或无星状体/Cep152中的酸性区域之间的相互作用来靶向母中心粒。在此，我们报道了秀丽隐杆线虫ZYG-1的CPB的晶体结构，其形成一个Z形二聚体，包含一个具有延伸碱性表面斑块的分子间β折叠。生化和体内分析表明，静电相互作用将ZYG-1 CPB碱性斑块对接至SPD-2衍生的酸性区域，以促进ZYG-1靶向和新中心粒组装。对果蝇Plk4（DmPlk4）CPB的不同晶体形式的分析表明，它也形成一个Z形二聚体。ZYG-1和DmPlk4 CPB的比较揭示了ZYG-1 CPB中的结构变化，这些变化赋予了其对SPD-2而非无星状体衍生的酸性区域的结合选择性。总体而言，我们的研究结果表明了一种保守机制，用于启动子中心粒组装的Plk4同源物的中心粒对接。
