Molecular architecture of the 40S⋅eIF1⋅eIF3 translation initiation complex.

Molecular architecture of the 40S⋅eIF1⋅eIF3 translation initiation complex.
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DOI:
10.1016/j.cell.2014.07.044
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发表时间:
2014-08-28
期刊:
影响因子:
64.5
通讯作者:
Ban N
Ban N
中科院分区:
生物学1区
文献类型:
--
作者:
Erzberger JP;Stengel F;Pellarin R;Zhang S;Schaefer T;Aylett CHS;Cimermančič P;Boehringer D;Sali A;Aebersold R;Ban N

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真核翻译起始需要将大型多蛋白 eIF3 复合物募集至 40S 核糖体亚基。我们展示了最小的六亚基酿酒酵母 eIF3 核心的所有主要成分的 X 射线结构。这些结构,加上电子显微镜重建、与质谱联用的交联以及综合结构建模,使我们能够在 40S⋅eIF1 复合体上定位和定向所有 eIF3 组件,揭示 eIF3 亚基的扩展、模块化排列。酵母eIF3以类似钳子的方式接合40S,完全包围40S,将关键起始因子定位在mRNA通道的两端,为翻译起始机制的招募、组装和调节提供平台。本文报道的 eIF3 成分的结构对于理解哺乳动物 43S 起始复合物以及 eIF3、40S 和丙型肝炎内部核糖体进入位点 RNA 的复合物的结构也具有重要意义。主要酵母 eIF3 成分和子复合物的 X 射线结构 交联与 40S⋅eIF1⋅eIF3 复合物的质谱分析相结合 综合建模揭示了 40S⋅eIF1⋅eIF3 复合物的结构 一种利用 X 射线结构、交联与质谱、电子显微镜和综合建模相结合的混合方法,产生了如何产生机制的见解 eIF3 协调翻译起始。
Eukaryotic translation initiation requires the recruitment of the large, multiprotein eIF3 complex to the 40S ribosomal subunit. We present X-ray structures of all major components of the minimal, six-subunit Saccharomyces cerevisiae eIF3 core. These structures, together with electron microscopy reconstructions, cross-linking coupled to mass spectrometry, and integrative structure modeling, allowed us to position and orient all eIF3 components on the 40S⋅eIF1 complex, revealing an extended, modular arrangement of eIF3 subunits. Yeast eIF3 engages 40S in a clamp-like manner, fully encircling 40S to position key initiation factors on opposite ends of the mRNA channel, providing a platform for the recruitment, assembly, and regulation of the translation initiation machinery. The structures of eIF3 components reported here also have implications for understanding the architecture of the mammalian 43S preinitiation complex and the complex of eIF3, 40S, and the hepatitis C internal ribosomal entry site RNA. X-ray structures of major yeast eIF3 components and subcomplexes Crosslinking coupled to mass-spectrometry analysis of 40S⋅eIF1⋅eIF3 complex Integrative modeling reveals architecture of 40S⋅eIF1⋅eIF3 complex A hybrid approach drawing on X-ray structures, crosslinking coupled to mass spectrometry, electron microscopy, and integrative modeling yields mechanistic insights into how eIF3 coordinates translation initiation.
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