Crystal Structure of the HCV IRES Central Domain Reveals Strategy for Start-Codon Positioning
Crystal Structure of the HCV IRES Central Domain Reveals Strategy for Start-Codon Positioning
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DOI：
10.1016/j.str.2011.08.002
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发表时间：
2011-10-12
期刊：
影响因子：
5.7
通讯作者：
Doudna, Jennifer A.
中科院分区：
文献类型：
--
作者：
Berry, Katherine E.;Waghray, Shruti;Doudna, Jennifer A.
丙型肝炎病毒蛋白的翻译需要位于病毒mRNA 5'非翻译区的内部核糖体进入位点（IRES）。丙型肝炎病毒（HCV）IRES的核心结构域包含一个整合在预测假结内的四向螺旋连接。该结构域是在翻译起始期间将mRNA起始密码子正确定位在40S核糖体亚基上所必需的。在这里，我们提出了这种RNA的晶体结构，揭示了一个复杂的双假结折叠，建立了四螺旋连接的两侧两个螺旋元件的对齐。该核心结构域的构象限制了开放阅读框定位在40 S核糖体亚基上的方向。这种结构，代表了HCV样IRES的最后一个主要结构域，在近原子分辨率下确定，为完整的HCV IRES及其与40 S核糖体亚基的相互作用的全面冷冻电子显微镜引导模型提供了基础。
Translation of hepatitis C viral proteins requires an internal ribosome entry site (IRES) located in the 5' untranslated region of the viral mRNA. The core domain of the hepatitis C virus (HCV) IRES contains a four-way helical junction that is integrated within a predicted pseudoknot. This domain is required for positioning the mRNA start codon correctly on the 40S ribosomal subunit during translation initiation. Here, we present the crystal structure of this RNA, revealing a complex double-pseudoknot fold that establishes the alignment of two helical elements on either side of the four-helix junction. The conformation of this core domain constrains the open reading frame's orientation for positioning on the 40S ribosomal subunit. This structure, representing the last major domain of HCV-like IRESs to be determined at near-atomic resolution, provides the basis for a comprehensive cryoelectron microscopy-guided model of the intact HCV IRES and its interaction with 40S ribosomal subunits.