Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A.
Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A.
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DOI：
10.1038/ncomms11952
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发表时间：
2016-06-16
影响因子：
16.6
通讯作者：
Görlich D
中科院分区：
文献类型：
--
作者：
Aksu M;Trakhanov S;Görlich D
XPO4是一种双向核转运受体，介导eIF5A和Smad3的核输出以及Sox2和SRY的输入。XPO4是如何识别这样一种货物的，目前还不得而知。在这里，我们介绍了在3.2 ä分辨率下的RanGTP·XPO4·eIF5A出口络合物的晶体结构。XPO4具有与CRM1相似的结构，但NES结合位点被遮挡，并且形成了一个新的相互作用位点，识别eIF5A的两个球状结构域。EIF5A含有亚硫氨酸，这是一种独特的具有两个正电荷的氨基酸，对细胞存活和翻译中的eIF5A功能是必不可少的。这种硫氨酸对接在XPO4的一个很深的酸性口袋中，因此是eIF5A复杂出口签名的关键元素。这进一步表明XPO4识别其他货物的方式不同，并说明了XPO4是如何以一种伴侣般的方式抑制核内eIF5A的不良相互作用的。XPO4将Sox2和其他蛋白质输入细胞核，同时输出eIF5A或SMAD3；它如何识别这些蛋白质一直不清楚。在这里，作者解析了RanGTP、XPO4和eIF5A复合体的晶体结构，并研究了XPO4如何识别其主要出口货物。
Xpo4 is a bidirectional nuclear transport receptor that mediates nuclear export of eIF5A and Smad3 as well as import of Sox2 and SRY. How Xpo4 recognizes such a variety of cargoes is as yet unknown. Here we present the crystal structure of the RanGTP·Xpo4·eIF5A export complex at 3.2 Å resolution. Xpo4 has a similar structure as CRM1, but the NES-binding site is occluded, and a new interaction site evolved that recognizes both globular domains of eIF5A. eIF5A contains hypusine, a unique amino acid with two positive charges, which is essential for cell viability and eIF5A function in translation. The hypusine docks into a deep, acidic pocket of Xpo4 and is thus a critical element of eIF5A's complex export signature. This further suggests that Xpo4 recognizes other cargoes differently, and illustrates how Xpo4 suppresses – in a chaperone-like manner – undesired interactions of eIF5A inside nuclei. Xpo4 imports Sox2 and other proteins into the cell nucleus, while exporting eIF5A or Smad3; how it recognizes these proteins has been unclear. Here, the authors solved the crystal structure of the RanGTP, Xpo4 and eIF5A complex and investigate how Xpo4 identifies its major export cargo.