Structural Basis for the Functional Coupling of the Alternative Splicing Factors Smu1 and RED.
Structural Basis for the Functional Coupling of the Alternative Splicing Factors Smu1 and RED.
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DOI：
10.1016/j.str.2016.03.016
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发表时间：
2016-05
期刊：
影响因子：
5.7
通讯作者：
A. Ulrich;J. Schulz;A. Kamprad;T. Schütze;M. Wahl
中科院分区：
文献类型：
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作者：
A. Ulrich;J. Schulz;A. Kamprad;T. Schütze;M. Wahl
Smu 1和RED蛋白共同参与了选择性剪接、有丝分裂和流感病毒感染的调节，但它们如何相互作用以及它们的多种细胞功能是否耦合尚不清楚。我们确定了Smu 1的N-末端区域和RED的中心区域稳定相互作用。结构分析表明Smu 1的RED结合区包含一个连接到核心结构域的N-末端LisH基序和一个折叠回LisH基序的C-末端α螺旋。Smu 1通过其LisH基序和C-末端α螺旋二聚化，并在RED结合后发生全局构象变化。在随后的异源四聚体Smu 1-RED复合物中，两个RED分子使用短α螺旋结合两个Smu 1核心结构域的疏水凹槽。我们的研究结果表明，Smu 1和RED如何形成一个功能模块，表现出有趣的相似性，转录辅阻遏复合物，安排多个额外的蛋白质-蛋白质相互作用位点接触剪接和/或染色质因子。
The proteins Smu1 and RED have been jointly implicated in the regulation of alternative splicing, mitosis, and influenza virus infection, but how they interact and whether their diverse cellular functions are coupled is unknown. We identified an N-terminal region of Smu1 and a central region of RED that stably interact. Structural analyses revealed that the RED-binding region of Smu1 contains an N-terminal LisH motif linked to a core domain and a C-terminal α helix that folds back onto the LisH motif. Smu1 dimerizes via its LisH motif and C-terminal α helix and undergoes global conformational changes upon RED binding. In the ensuing hetero-tetrameric Smu1-RED complex, two molecules of RED use short α helices to bind hydrophobic grooves of two Smu1 core domains. Our results show how Smu1 and RED form a functional module that exhibits intriguing similarities to transcriptional co-repressor complexes, arranging multiple additional protein-protein interaction sites for contacting splicing and/or chromatin factors.