Structure of a Cytoplasmic 11-Subunit RNA Exosome Complex.
Structure of a Cytoplasmic 11-Subunit RNA Exosome Complex.
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DOI：
10.1016/j.molcel.2016.05.028
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发表时间：
2016-07-07
期刊：
影响因子：
16
通讯作者：
Conti E
中科院分区：
文献类型：
--
作者：
Kowalinski E;Kögel A;Ebert J;Reichelt P;Stegmann E;Habermann B;Conti E
RNA外泌体复合体与核和细胞质辅助因子结合，介导多种转录本的衰变、监视或加工。在细胞质中，外泌体的保守核心（Exo10）与保守的Ski复合物一起起作用。酿酒酵母Exo10与Ski的相互作用不是直接的，而是需要一个桥接辅因子Ski7。本文报道了S. cerevisiae Exo10与Ski7相互作用结构域结合的2.65 Å分辨率结构。广泛的疏水相互作用合理化了该复合物的高亲和力和稳定性，指出Ski7是细胞质外泌体的组成部分。尽管缺乏序列同源性，细胞质Ski7和核Rrp6使用相似的表面和识别基序结合Exo10。酵母复合体中相互作用残基的知识使我们能够鉴定出人类HBS1-Like的剪接变体为ski7样外泌体结合蛋白，揭示了这种细胞质辅助因子的进化保守性。酵母外显体与Ski7的结合具有低纳摩尔亲和力和广泛的相互作用，sk7外显体结合域在识别Csl4、Mtr3和Rrp43亚基时折叠，sk7和Rrp6缺乏序列同源性，但与外显体形成类似的界面。酵母sk7的外显体界面残基在人类Hbs1L异构体3中是保守的。Kowalinski等（2016）表明酵母外显体核心复合物类似地识别细胞质辅因子Ski7和核辅因子Rrp6。通过结构分析，他们确定HSB1-Like的剪接变体是长期寻找的人类ski7样外泌体结合辅因子。
The RNA exosome complex associates with nuclear and cytoplasmic cofactors to mediate the decay, surveillance, or processing of a wide variety of transcripts. In the cytoplasm, the conserved core of the exosome (Exo10) functions together with the conserved Ski complex. The interaction of S. cerevisiae Exo10 and Ski is not direct but requires a bridging cofactor, Ski7. Here, we report the 2.65 Å resolution structure of S. cerevisiae Exo10 bound to the interacting domain of Ski7. Extensive hydrophobic interactions rationalize the high affinity and stability of this complex, pointing to Ski7 as a constitutive component of the cytosolic exosome. Despite the absence of sequence homology, cytoplasmic Ski7 and nuclear Rrp6 bind Exo10 using similar surfaces and recognition motifs. Knowledge of the interacting residues in the yeast complexes allowed us to identify a splice variant of human HBS1-Like as a Ski7-like exosome-binding protein, revealing the evolutionary conservation of this cytoplasmic cofactor. The yeast exosome binds Ski7 with low nanomolar affinity and extensive interactions The Ski7 exosome-binding domain folds upon recognizing Csl4, Mtr3, and Rrp43 subunits Ski7 and Rrp6 lack sequence homology but form a similar interface with the exosome The exosome interface residues of yeast Ski7 are conserved in human Hbs1L isoform 3 Kowalinski et al. (2016) show that the yeast exosome core complex recognizes the cytoplasmic cofactor Ski7 and the nuclear cofactor Rrp6 similarly. Through structural analyses, they identify a splice variant of HSB1-Like as the long-sought Ski7-like exosome binding cofactor in humans.