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首页> 外文期刊>Journal of Molecular Biology >HnRNP Al Alters the Structure of a Conserved Enterovirus IRES Domain to Stimulate Viral Translation
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HnRNP Al Alters the Structure of a Conserved Enterovirus IRES Domain to Stimulate Viral Translation

机译：HNRNP AL改变了保守的肠病毒IRES结构域的结构，刺激病毒翻译

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摘要

Enteroviruses use a type I Internal Ribosome Entry Site (IRES) structure to facilitate protein synthesis and promote genome replication. Type I IRES elements require auxiliary host proteins to organize RNA structure for 40S ribosomal subunit assembly. Heterogeneous nuclear ribonucleoprotein Al stimulates enterovirus 71 (EV71) translation in part through specific interactions with its stem loop II (SLII) IRES domain. Here, we determined a conjoined NMR-small angle x-ray scattering structure of the EV71 SLII domain and a mutant that significantly attenuates viral replication by abrogating hnRNP Al interactions. Native SLII adopts a locally compact structure wherein stacking interactions in a conserved 5'-AUAGC-3' bulge preorganize the adjacent helices at nearly orthogonal orientations. Mutating the bulge sequence to 5'-ACCCC-3' ablates base stacking in the loop and globally reorients the SLII structure. Biophysical titrations reveal that the 5'-AUAGC-3' bulge undergoes a conformational change to assemble a functional hnRNP Al RNA complex. Importantly, IRES mutations that delete the bulge impair viral translation and completely inhibit replication. Thus, this work provides key details into how an EV71 IRES structure adapts to hijack a cellular protein, and it suggests that the SLII domain is a potential target for antiviral therapy. (C) 2017 Elsevier Ltd. All rights reserved.
机译：肠病毒使用I型内部核糖体进入部位（IRES）结构来促进蛋白质合成并促进基因组复制。 I型IRES元素需要辅助宿主蛋白来组织40s核糖体亚基组件的RNA结构。通过与其茎环II（SLII）IRES结构域的特异性相互作用，异质核核糖核糖核酸蛋白Al刺激肠道病毒71（EV71）平移。这里，我们确定了EV71 SLII结构域的联合NMR小角X射线散射结构和通过消除HNRNP Al相互作用显着衰减病毒复制。天然SLII采用局部紧凑的结构，其中在节省的5'-auagc-3'凸起中堆叠相互作用，以几乎正交的取向预组化相邻螺旋。将凸出序列突变为5'-ACCC-3'堆叠在循环中的堆叠，并且全局重新定位SLII结构。生物物理滴定表明，5'-auagc-3'凸起经历构象变化以组装功能性HNRNP Al RNA复合物。重要的是，删除凸起的IRES突变损害病毒翻译并完全抑制复制。因此，这项工作提供了关键细节，进入EV71 IRES结构如何适应劫持细胞蛋白质，并且表明SLII结构域是抗病毒治疗的潜在目标。 （c）2017 Elsevier Ltd.保留所有权利。

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