Cook Atlanta G, Fukuhara Noemi, Jinek Martin, Conti Elena
Structural Cell Biology, MPI for Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Nature. 2009 Sep 3;461(7260):60-5. doi: 10.1038/nature08394.
Transfer RNAs are among the most ubiquitous molecules in cells, central to decoding information from messenger RNAs on translating ribosomes. In eukaryotic cells, tRNAs are actively transported from their site of synthesis in the nucleus to their site of function in the cytosol. This is mediated by a dedicated nucleo-cytoplasmic transport factor of the karyopherin-beta family (Xpot, also known as Los1 in Saccharomyces cerevisiae). Here we report the 3.2 A resolution structure of Schizosaccharomyces pombe Xpot in complex with tRNA and RanGTP, and the 3.1 A structure of unbound Xpot, revealing both nuclear and cytosolic snapshots of this transport factor. Xpot undergoes a large conformational change on binding cargo, wrapping around the tRNA and, in particular, binding to the tRNA 5' and 3' ends. The binding mode explains how Xpot can recognize all mature tRNAs in the cell and yet distinguish them from those that have not been properly processed, thus coupling tRNA export to quality control.
转运RNA是细胞中最为普遍存在的分子之一，对于在翻译核糖体上解码信使RNA中的信息至关重要。在真核细胞中，转运RNA从细胞核中的合成位点被主动运输到细胞质中的功能位点。这一过程由核转运蛋白β家族的一种特定核质运输因子介导（Xpot，在酿酒酵母中也被称为Los1）。在此，我们报告了粟酒裂殖酵母Xpot与转运RNA及RanGTP复合物的3.2埃分辨率结构，以及未结合状态下Xpot的3.1埃结构，揭示了该运输因子在细胞核和细胞质中的状态。Xpot在结合货物时会发生巨大的构象变化，围绕转运RNA缠绕，特别是与转运RNA的5'端和3'端结合。这种结合模式解释了Xpot如何能够识别细胞中的所有成熟转运RNA，同时又能将它们与未经过正确加工的转运RNA区分开来，从而将转运RNA的输出与质量控制联系起来。
