Several Phenylalanine-Glycine Motives in the Nucleoporin Nup214 Are Essential for Binding of the Nuclear Export Receptor CRM1*
Several Phenylalanine-Glycine Motives in the Nucleoporin Nup214 Are Essential for Binding of the Nuclear Export Receptor CRM1*
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DOI：
10.1074/jbc.m112.433243
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发表时间：
2012-12
期刊：
影响因子：
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通讯作者：
S. Roloff;Christiane Spillner;R. Kehlenbach
中科院分区：
文献类型：
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作者：
S. Roloff;Christiane Spillner;R. Kehlenbach
背景：Nup214与核出口受体CRM1相互作用，促进某些货物的出口。结果：c端区域的几个FG动机参与了CRM1的结合。结论：CRM1与其他转运受体一样，与核孔蛋白有多次接触。意义：阐明核孔蛋白-受体相互作用的细节对于我们理解转运复合物通过核孔的过渡过程至关重要。含有苯丙氨酸甘氨酸（FG）重复序列的核孔蛋白与转运受体结合，介导转运复合物跨核孔复合物（NPC）的易位，在核胞质转运中发挥重要作用。Nup214/CAN是一种核孔蛋白，存在于鼻咽癌细胞质侧，与输入和输出受体相互作用。在功能分析中，Nup214的显性阴性片段抑制crm1依赖的核输出，因为输出受体成为限速的。相比之下，几种核输入途径不受Nup214片段的影响。我们现在详细描述了Nup214的crm1结合区，并确定了这种相互作用所需的几个FG动机。我们的研究结果支持一个模型，即CRM1像其他转运受体一样，通过多个结合位点与FG-Nups接触。
Background: Nup214 interacts with the nuclear export receptor CRM1 and promotes export of certain cargos. Results: Several FG motives in the C-terminal region participate in CRM1 binding. Conclusion: CRM1, like other transport receptors, makes multiple contacts to nucleoporins. Significance: Elucidation of the details of nucleoporin-receptor interactions is essential for our understanding of the transition process of transport complexes through the nuclear pore. Nucleoporins containing phenylalanine glycine (FG) repeats play an important role in nucleocytoplasmic transport as they bind to transport receptors and mediate translocation of transport complexes across the nuclear pore complex (NPC). Nup214/CAN, a nucleoporin that is found at the cytoplasmic side of the NPC, interacts with both import and export receptors. In functional assays, dominant-negative fragments of Nup214 inhibited CRM1-dependent nuclear export, as the export receptor became rate-limiting. Several nuclear import pathways, by contrast, were not affected by the Nup214 fragments. We now characterize the CRM1-binding region of Nup214 in detail and identify several FG motives that are required for this interaction. Our results support a model where CRM1, like other transport receptors, contacts FG-Nups via multiple binding sites.