Nuclear Import Mechanism of the EJC Component Mago-Y14 Revealed by Structural Studies of Importin 13
Nuclear Import Mechanism of the EJC Component Mago-Y14 Revealed by Structural Studies of Importin 13
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DOI：
10.1016/j.molcel.2010.01.007
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发表时间：
2010-01-29
期刊：
影响因子：
16
通讯作者：
Conti, Elena
中科院分区：
文献类型：
--
作者：
Bono, Fulvia;Cook, Atlanta G.;Conti, Elena
Mago和Y14是外显子连接复合物（EJC）的核心组分，EJC是人类无义介导的mRNA衰变和果蝇mRNA定位的核心组件。Mago-Y14异源二聚体在细胞核和细胞质之间穿梭，在细胞核中它被装载到特定的mRNA上，在细胞质中它在翻译调节中起作用。异二聚体通过Importin 13（Imp 13）输入回细胞核，Importin 13是转运因子核粒蛋白β家族的成员。我们已经阐明了Mago-Y14核进口周期的结构基础。果蝇Imp 13-Mago-Y14复合物的3.35埃结构表明Imp 13形成环状分子，使人想起Crm 1，并以保守的相互作用表面包围Mago-Y14货物。与RanGTP结合的人Imp 13的2.8埃结构揭示了Mago-Y14如何通过空间位阻机制在细胞核中释放。这两种结构的比较表明，这种不寻常的karyopherin可能在双向核质运输的功能。
Mago, and Y14 are core components of the exon junction complex (EJC), an assembly central to nonsense-mediated mRNA decay in humans and mRNA localization in flies. The Mago-Y14 heterodimer shuttles between the nucleus, where it is loaded onto specific mRNAs, and the cytoplasm, where it functions in translational regulation. The heterodimer is imported back into the nucleus by Importin 13 (Imp13), a member of the karyopherin-beta family of transport factors. We have elucidated the structural basis of the Mago-Y14 nuclear import cycle. The 3.35 angstrom structure of the Drosophila Imp13-Mago-Y14 complex shows that Imp13 forms a ring-like molecule, reminiscent of Crm1, and encircles the Mago-Y14 cargo with a conserved interaction surface. The 2.8 angstrom structure of human Imp13 bound to RanGTP reveals how Mago-Y14 is released in the nucleus by a steric hindrance mechanism. Comparison of the two structures suggests how this unusual karyopherin might function in bidirectional nucleocytoplasmic transport.