The RanBP2/RanGAP1*SUMO1/Ubc9 SUMO E3 ligase is a disassembly machine for Crm1-dependent nuclear export complexes.,Nature Communications

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The RanBP2/RanGAP1*SUMO1/Ubc9 SUMO E3 ligase is a disassembly machine for Crm1-dependent nuclear export complexes.
Nature Communications ( IF 14.7 ) Pub Date : 2016-05-10 , DOI: 10.1038/ncomms11482
Tobias Ritterhoff _{1,

2} , Hrishikesh Das _{1,

3} , Götz Hofhaus ₃ , Rasmus R Schröder ₃ , Annette Flotho ₁ , Frauke Melchior ₁

Affiliation

Continuous cycles of nucleocytoplasmic transport require disassembly of transport receptor/Ran-GTP complexes in the cytoplasm. A basic disassembly mechanism in all eukaryotes depends on soluble RanGAP and RanBP1. In vertebrates, a significant fraction of RanGAP1 stably interacts with the nucleoporin RanBP2 at a binding site that is flanked by FG-repeats and Ran-binding domains, and overlaps with RanBP2's SUMO E3 ligase region. Here, we show that the RanBP2/RanGAP1*SUMO1/Ubc9 complex functions as an autonomous disassembly machine with a preference for the export receptor Crm1. We describe three in vitro reconstituted disassembly intermediates, which show binding of a Crm1 export complex via two FG-repeat patches, cargo-release by RanBP2's Ran-binding domains and retention of free Crm1 at RanBP2 after Ran-GTP hydrolysis. Intriguingly, all intermediates are compatible with SUMO E3 ligase activity, suggesting that the RanBP2/RanGAP1*SUMO1/Ubc9 complex may link Crm1- and SUMO-dependent functions.

中文翻译：

RanBP2/RanGAP1*SUMO1/Ubc9 SUMO E3 连接酶是 Crm1 依赖性核输出复合物的拆卸机器。

核质转运的连续循环需要细胞质中转运受体/Ran-GTP复合物的分解。所有真核生物的基本分解机制都依赖于可溶性 RanGAP 和 RanBP1。在脊椎动物中，RanGAP1 的很大一部分在结合位点与核孔蛋白 RanBP2 稳定地相互作用，该结合位点两侧是 FG 重复序列和 Ran 结合域，并且与 RanBP2 的 SUMO E3 连接酶区域重叠。在这里，我们展示了 RanBP2/RanGAP1*SUMO1/Ubc9 复合物作为自主拆卸机器的功能，并且优先考虑输出受体 Crm1。我们描述了三种体外重构的拆卸中间体，其显示通过两个 FG 重复片段结合 Crm1 输出复合物、RanBP2 的 Ran 结合域释放货物以及 Ran-GTP 水解后游离 Crm1 保留在 RanBP2 上。有趣的是，所有中间体都与 SUMO E3 连接酶活性兼容，这表明 RanBP2/RanGAP1*SUMO1/Ubc9 复合物可能连接 Crm1 和 SUMO 依赖性功能。

更新日期：2016-05-13

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