Department of Cellular Logistics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Department of Cellular Logistics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
J Cell Biol. 2019 Jun 3;218(6):1839-1852. doi: 10.1083/jcb.201812093. Epub 2019 Apr 25.
Importins ferry proteins into nuclei while exportins carry cargoes to the cytoplasm. In the accompanying paper in this issue (Vera Rodriguez et al. 2019. https://doi.org/10.1083/jcb.201812091), we discovered that Pdr6 is a biportin that imports, e.g., the SUMO E2 ligase Ubc9 while depleting the translation factor eIF5A from the nuclear compartment. In this paper, we report the structures of key transport intermediates, namely, of the Ubc9•Pdr6 import complex, of the RanGTP•Pdr6 heterodimer, and of the trimeric RanGTP•Pdr6•eIF5A export complex. These revealed nonlinear transport signals, chaperone-like interactions, and how the RanGTPase system drives Pdr6 to transport Ubc9 and eIF5A in opposite directions. The structures also provide unexpected insights into the evolution of transport selectivity. Specifically, they show that recognition of Ubc9 by Pdr6 differs fundamentally from that of the human Ubc9-importer Importin 13. Likewise, Pdr6 recognizes eIF5A in a nonhomologous manner compared with the mammalian eIF5A-exporter Exportin 4. This suggests that the import of Ubc9 and active nuclear exclusion of eIF5A evolved in different eukaryotic lineages more than once and independently from each other.
输入蛋白通过输入蛋白将蛋白质运进细胞核，输出蛋白则将货物运出细胞质。在本期的相关论文中（Vera Rodriguez 等人，2019 年，https://doi.org/10.1083/jcb.201812091），我们发现 Pdr6 是一种双向蛋白转运体，它可以将 SUMO E2 连接酶 Ubc9 等物质输入细胞核，同时将翻译因子 eIF5A 从核内区室中耗尽。在本文中，我们报告了关键运输中间产物的结构，即 Ubc9•Pdr6 输入复合物、RanGTP•Pdr6 异二聚体和三聚物 RanGTP•Pdr6•eIF5A 输出复合物的结构。这些结构揭示了非线性运输信号、分子伴侣样相互作用，以及 RanGTPase 系统如何驱动 Pdr6 以相反的方向转运 Ubc9 和 eIF5A。这些结构还为运输选择性的进化提供了意想不到的见解。具体来说，它们表明 Pdr6 对 Ubc9 的识别与人类 Ubc9 输入蛋白 Importin 13 的识别有根本的不同。同样，与哺乳动物 eIF5A 输出蛋白 Exportin 4 相比，Pdr6 以非同源的方式识别 eIF5A。这表明 Ubc9 的输入和 eIF5A 的主动核排斥在不同的真核生物谱系中独立地多次进化而来。
