The structural basis of Miranda-mediated Staufen localization during Drosophila neuroblast asymmetric division.
The structural basis of Miranda-mediated Staufen localization during Drosophila neuroblast asymmetric division.
复制标题
果蝇成神经细胞不对称分裂过程中米兰达介导的诗道芬定位的结构基础
DOI：
10.1038/ncomms9381
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发表时间：
2015-10-01
影响因子：
16.6
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Jia M;Shan Z;Yang Y;Liu C;Li J;Luo ZG;Zhang M;Cai Y;Wen W;Wang W
在果蝇神经母细胞(NBS)的不对称分裂过程中，支架米兰达(MIRA)协调包括Staufen(Stau)在内的细胞命运决定因素的亚细胞分布，并将它们分离到神经节母细胞(GMC)中。在这里，我们证明了Stau的第五个双链RNA(DsRNA)结合结构域(DsRBD5)是与Mira货物结合结构域(CBD)的卷曲线圈区域结合的必要条件和充分条件。Mira514-595/Stau dsRBD5复合体的晶体结构表明，MIRA形成一个拉长的平行螺旋二聚体，两个DsRBD5通过暴露的β片面对称地结合到MIRA二聚体上，揭示了dsRBD的一种未知的蛋白质相互作用模式。我们进一步证明，在果蝇NB不对称分裂过程中，Mira-Stau dsRBD5相互作用是导致Stau不对称定位的原因。最后，我们发现CBD介导的二聚体组装可能是Mira识别和转移包括脑瘤(Brat)在内的其他货物的共同要求。
During the asymmetric division of Drosophila neuroblasts (NBs), the scaffold Miranda (Mira) coordinates the subcellular distribution of cell-fate determinants including Staufen (Stau) and segregates them into the ganglion mother cells (GMCs). Here we show the fifth double-stranded RNA (dsRNA)-binding domain (dsRBD5) of Stau is necessary and sufficient for binding to a coiled-coil region of Mira cargo-binding domain (CBD). The crystal structure of Mira514–595/Stau dsRBD5 complex illustrates that Mira forms an elongated parallel coiled-coil dimer, and two dsRBD5 symmetrically bind to the Mira dimer through their exposed β-sheet faces, revealing a previously unrecognized protein interaction mode for dsRBDs. We further demonstrate that the Mira–Stau dsRBD5 interaction is responsible for the asymmetric localization of Stau during Drosophila NB asymmetric divisions. Finally, we find the CBD-mediated dimer assembly is likely a common requirement for Mira to recognize and translocate other cargos including brain tumour (Brat).