Conserved β-Hairpin Recognition by the GYF Domains of Smy2 and GIGYF2 in mRNA Surveillance and Vesicular Transport Complexes
Conserved β-Hairpin Recognition by the GYF Domains of Smy2 and GIGYF2 in mRNA Surveillance and Vesicular Transport Complexes
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DOI：
10.1016/j.str.2010.04.020
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发表时间：
2010-08-11
期刊：
影响因子：
5.7
通讯作者：
Freund, Christian
中科院分区：
文献类型：
--
作者：
Ash, Miriam-Rose;Faelber, Katja;Freund, Christian
肌球蛋白2蛋白的酵母抑制因子（Smy 2）通过识别富含脯氨酸的序列（PRS）与mRNA加工蛋白相互作用。在这里，我们描述的晶体结构的GYF结构域的Smy 2与PRS从酵母分支点结合蛋白（BBP/ScSF 1）。复合物的形成需要配体的中心PPGL基序的β-发夹被结构域中的延伸的疏水裂缝所容纳-这是在人蛋白GIGYF 2中保持的特异性特征。结合PRS位点抑制的SILAC/MS实验表明，Smy 2与Ccr 4-NOT去腺苷酶复合物相关，而GIGYF 2不仅与mRNA监视因子相互作用，而且与囊泡转运蛋白和Atrophin-1相互作用。GIGYF 2与COPII囊泡蛋白相关，并定位于静息细胞中的ER和高尔基体，而环境挑战驱使GIGYF 2进入应激颗粒。目前的研究突出了PRS识别Smy 2型GYF结构域的结构基础，并暗示Smy 2和GIGYF 2在mRNA加工和分泌途径。
The yeast suppressor of myosin 2 protein (Smy2) interacts with mRNA-processing proteins through recognition of proline-rich sequences (PRS). Here, we describe the crystal structure of the GYF domain of Smy2 in association with a PRS from the yeast branch point binding protein (BBP/ScSF1). Complex formation requires that the beta-hairpin of the central PPGL motif of the ligand is accommodated by an extended hydrophobic cleft in the domain-a specificity feature that is maintained in the human protein GIGYF2. SILAC/MS experiments in combination with PRS site inhibition show that Smy2 associates with the Ccr4-NOT deadenylase complex, whereas GIGYF2 interacts not only with mRNA surveillance factors, but also with vesicular transport proteins and Atrophin-1. GIGYF2 is shown to associate with COPII-vesicle proteins and localize to the ER and Golgi in resting cells, whereas environmental challenge drives GIGYF2 into stress granules. The current study highlights the structural basis for PRS recognition by Smy2-type GYF domains, and implicates Smy2 and GIGYF2 in both mRNA processing and the secretory pathway.