Crystal Structure of the Nuclear Export Receptor CRM1 in Complex with Snurportin1 and RanGTP
Crystal Structure of the Nuclear Export Receptor CRM1 in Complex with Snurportin1 and RanGTP
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DOI：
10.1126/science.1173388
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发表时间：
2009-05-22
期刊：
影响因子：
56.9
通讯作者：
Ficner, Ralf
中科院分区：
文献类型：
--
作者：
Monecke, Thomas;Guettler, Thomas;Ficner, Ralf
CRM1介导众多不相关货物的核输出，这些货物可能携带富含亮氨酸的短核输出信号或包含折叠结构域的输出特征序列。到目前为止，CRM1如何识别如此多样的货物一直是未知的。在此我们展示了分辨率为2.5埃的SPN1·CRM1·RanGTP输出复合物的晶体结构（其中SPN1是核输入蛋白1，RanGTP是结合鸟苷5' - 三磷酸的Ran）。SPN1是一种核输入衔接蛋白，用于细胞质中组装的、带有m(3)G帽的剪接体U snRNP（小核核糖核蛋白）。该结构显示了CRM1如何特异性地将无货物形式的SPN1送回细胞质。广泛的接触区域包括SPN1氨基末端的五个疏水残基，它们嵌入CRM1的一个疏水裂隙中，以及CRM1与m3G帽结合结构域和SPN1羧基末端残基的众多亲水接触。该结构表明RanGTP仅通过输出蛋白的长程构象变化促进货物与CRM1的结合。
CRM1 mediates nuclear export of numerous unrelated cargoes, which may carry a short leucine-rich nuclear export signal or export signatures that include folded domains. How CRM1 recognizes such a variety of cargoes has been unknown up to this point. Here we present the crystal structure of the SPN1.CRM1.RanGTP export complex at 2.5 angstrom resolution (where SPN1 is snurportin1 and RanGTP is guanosine 5' triphosphate-bound Ran). SPN1 is a nuclear import adapter for cytoplasmically assembled, m(3)G-capped spliceosomal U snRNPs (small nuclear ribonucleoproteins). The structure shows how CRM1 can specifically return the cargo-free form of SPN1 to the cytoplasm. The extensive contact area includes five hydrophobic residues at the SPN1 amino terminus that dock into a hydrophobic cleft of CRM1, as well as numerous hydrophilic contacts of CRM1 to m3G cap-binding domain and carboxyl-terminal residues of SPN1. The structure suggests that RanGTP promotes cargo-binding to CRM1 solely through long-range conformational changes in the exportin.