Institute for Protein Research, Osaka University, 3-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Institute for Protein Research, Osaka University, 3-2 Yamada-oka, Suita, Osaka 565-0871, Japan; Department of Life Science, University of Hyogo, 3-2-1 Koto, Kamighori, Akoh, Hyogo 678-1297, Japan.
Structure. 2018 Oct 2;26(10):1393-1398.e2. doi: 10.1016/j.str.2018.06.014. Epub 2018 Aug 9.
In the nucleus, RanGTP binding to importin dissociates the cargo. On the other hand, RanGTP enables exportin to bind export cargo and form the export complex by each exportin's own cargo selection mechanism. Here, we present two X-ray structures for Exportin-5 (Exp-5) alone and Exp-5:RanGTP intermediate complex. The structure of Exp-5 adopts a ring-shaped closed conformation by C-terminal anchor residues 1,167-1,179, interacting with N-terminal heat repeats 4-9. The closed form of Exp-5 is important for the stability of the cargo-free state. Interaction between Exp-5 and RanGTP induces elimination of intramolecular contacts of the C-terminal anchor. A large movement of N-terminal 1-9th heat repeats and C-terminal 19-20th heat repeats creates an open space for RanGTP accommodation. Exp-5 in Exp-5:RanGTP and Exp-5:RanGTP:pre-miRNA adopts the same conformation. RanGTP binding to Exp-5 creates a selective molecular cage area for accepting its cargoes, such as small double-stranded RNAs, without conformational change in Exp-5:RanGTP.
在核内，RanGTP 与导入蛋白结合将货物分离。另一方面，RanGTP 使输出蛋白能够结合输出货物，并通过每个输出蛋白自身的货物选择机制形成输出复合物。在这里，我们展示了单独的 Exportin-5（Exp-5）和 Exp-5:RanGTP 中间复合物的两个 X 射线结构。Exp-5 的结构通过 C 末端锚定残基 1,167-1,179 采用环形封闭构象，与 N 末端热重复 4-9 相互作用。Exp-5 的封闭形式对于无货物状态的稳定性很重要。Exp-5 与 RanGTP 的相互作用诱导 C 末端锚定的分子内接触消除。N 末端 1-9 个热重复和 C 末端 19-20 个热重复的大运动为 RanGTP 容纳创造了一个开放空间。Exp-5 在 Exp-5:RanGTP 和 Exp-5:RanGTP:pre-miRNA 中采用相同的构象。RanGTP 与 Exp-5 的结合为接受其货物（如小双链 RNA）创造了一个选择性的分子笼区域，而 Exp-5:RanGTP 没有构象变化。
