Structure of a human 48S translational initiation complex

Structure of a human 48S translational initiation complex
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DOI:
10.1126/science.aba4904
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发表时间:
2020-09-04
期刊:
影响因子:
56.9
通讯作者:
Ramakrishnan, V
Ramakrishnan, V
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Querido, Jailson Brito;Sokabe, Masaaki;Ramakrishnan, V

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翻译起始的关键步骤是43S前起始复合物被帽结合复合物[真核起始因子4F(eIF4F)]在信使RNA(mRNA)的5'末端募集以形成48S起始复合物(即,48S)。48 S然后沿着mRNA扫描以定位起始密码子。为了了解所涉及的机制,我们使用冷冻电子显微镜来确定重组人48S的结构。该结构揭示了翻译起始复合物组装的早期事件,以及eIF4F如何与43S中mRNA出口通道附近的eIF3亚基相互作用。eIF4F的位置与mRNA募集的开槽模型一致,并表明下游mRNA至少部分地通过在扫描期间被“拉”过40S亚基而解绕。
A key step in translational initiation is the recruitment of the 43S preinitiation complex by the cap-binding complex [eukaryotic initiation factor 4F (eIF4F)] at the 5' end of messenger RNA (mRNA) to form the 48S initiation complex (i.e., the 48S). The 48S then scans along the mRNA to locate a start codon. To understand the mechanisms involved, we used cryo-electron microscopy to determine the structure of a reconstituted human 48S. The structure reveals insights into early events of translation initiation complex assembly, as well as how eIF4F interacts with subunits of eIF3 near the mRNA exit channel in the 43S. The location of eIF4F is consistent with a slotting model of mRNA recruitment and suggests that downstream mRNA is unwound at least in part by being "pulled" through the 40S subunit during scanning.