Crystal structure of an RNA-bound 11-subunit eukaryotic exosome complex
Crystal structure of an RNA-bound 11-subunit eukaryotic exosome complex
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DOI：
10.1038/nature11870
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发表时间：
2013-03-07
期刊：
影响因子：
64.8
通讯作者：
Conti, Elena
中科院分区：
文献类型：
--
作者：
Makino, Debora Lika;Baumgaertner, Marc;Conti, Elena
外切体是真核生物中主要的3' - 5' RNA降解复合物。酵母外切体（Exo - 10）普遍存在的核心由9个无催化活性的亚基（Exo - 9）和一个有活性的核糖核酸酶Rrp44组成。在细胞核中，Exo - 10核心招募另一种核酸酶Rrp6。在此，我们结晶出了一个约440千道尔顿的酿酒酵母Exo - 10复合物，它与Rrp6的一个羧基末端区域以及一个具有31个核糖核苷酸3'突出端的RNA双链体结合。2.8埃分辨率的结构显示了RNA是如何通过一个解旋孔以单链构象被导入Exo - 9通道的。Rrp44呈现一种闭合构象，并捕获从Exo - 9侧面出来的RNA 3'末端。Exo - 9亚基以不依赖序列的相互作用结合RNA，这让人联想到古菌外切体。3' - 5' RNA降解复合物的底物结合和通道机制在所有生命领域中都是保守的。
The exosome is the major 3'-5' RNA-degradation complex in eukaryotes. The ubiquitous core of the yeast exosome (Exo-10) is formed by nine catalytically inert subunits (Exo-9) and a single active RNase, Rrp44. In the nucleus, the Exo-10 core recruits another nuclease, Rrp6. Here we crystallized an approximately 440-kilodalton complex of Saccharomyces cerevisiae Exo-10 bound to a carboxy-terminal region of Rrp6 and to an RNA duplex with a 3'-overhang of 31 ribonucleotides. The 2.8 angstrom resolution structure shows how RNA is funnelled into the Exo-9 channel in a single-stranded conformation by an unwinding pore. Rrp44 adopts a closed conformation and captures the RNA 3'-end that exits from the side of Exo-9. Exo-9 subunits bind RNA with-sequence-unspecific interactions reminiscent of archaeal exosomes. The substrate binding and channelling mechanisms of 3'-5' RNA degradation complexes are conserved in all kingdoms of life.