The structural basis of Edc3- and Scd6-mediated activation of the Dcp1:Dcp2 mRNA decapping complex
The structural basis of Edc3- and Scd6-mediated activation of the Dcp1:Dcp2 mRNA decapping complex
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DOI：
10.1038/emboj.2011.408
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发表时间：
2012-01-18
期刊：
影响因子：
11.4
通讯作者：
Sprangers, Remco
中科院分区：
文献类型：
--
作者：
Fromm, Simon A.;Truffault, Vincent;Sprangers, Remco
Dcp1:Dcp2 脱帽复合物催化 mRNA 5' 帽结构的去除。激活蛋白，包括 Edc3（脱帽 3 的增强子），可调节其活性。在这里，我们解析了酵母 Edc3 LSm 结构域与来自 Dcp2 的短螺旋富含亮氨酸基序 (HLM) 的复合物的结构。该基序以前所未有的方式与单体 Edc3 LSm 结构域相互作用，并识别非规范的结合表面。根据该结构，我们在 Dcp2 的无序 C 末端延伸中鉴定出了可以与 Edc3 相互作用的其他 HLM。此外，Edc3 相关蛋白 Scd6 的 LSm 结构域与 Edc3 竞争与这些 HLM 的相互作用。我们发现 Edc3 和 Scd6 都可以在体外刺激脱盖，推测是通过阻止 Dcp1:Dcp2 复合物采用非活性构象来实现的。此外，我们还表明，Dcp2 中的 C 端 HLM 对于 Dcp1:Dcp2 脱帽复合物在体内定位到 P 体是必需的。出乎意料的是，与酵母相反，在后生动物中，HLM 存在于 Dcp1 中，这表明 mRNA 脱帽调控的细节在整个进化过程中发生了变化。 EMBO 杂志 (2012) 31, 279-290。 doi：10.1038/emboj.2011.408； 2011 年 11 月 15 日在线发布
The Dcp1:Dcp2 decapping complex catalyses the removal of the mRNA 5' cap structure. Activator proteins, including Edc3 (enhancer of decapping 3), modulate its activity. Here, we solved the structure of the yeast Edc3 LSm domain in complex with a short helical leucine-rich motif (HLM) from Dcp2. The motif interacts with the monomeric Edc3 LSm domain in an unprecedented manner and recognizes a noncanonical binding surface. Based on the structure, we identified additional HLMs in the disordered C-terminal extension of Dcp2 that can interact with Edc3. Moreover, the LSm domain of the Edc3-related protein Scd6 competes with Edc3 for the interaction with these HLMs. We show that both Edc3 and Scd6 stimulate decapping in vitro, presumably by preventing the Dcp1:Dcp2 complex from adopting an inactive conformation. In addition, we show that the C-terminal HLMs in Dcp2 are necessary for the localization of the Dcp1:Dcp2 decapping complex to P-bodies in vivo. Unexpectedly, in contrast to yeast, in metazoans the HLM is found in Dcp1, suggesting that details underlying the regulation of mRNA decapping changed throughout evolution. The EMBO Journal (2012) 31, 279-290. doi:10.1038/emboj.2011.408; Published online 15 November 2011