The eukaryotic translation initiation factors eIF1 and eIF1A induce an open conformation of the 40S ribosome
The eukaryotic translation initiation factors eIF1 and eIF1A induce an open conformation of the 40S ribosome
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DOI：
10.1016/j.molcel.2007.03.018
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发表时间：
2007-04-13
期刊：
影响因子：
16
通讯作者：
Ramakrishnan, V.
中科院分区：
文献类型：
--
作者：
Passmore, Lori A.;Schmeing, T. Martin;Ramakrishnan, V.
翻译起始是起始tRNA和mRNA的起始密码子位于核糖体P位点的过程。在真核生物中，最初的步骤之一涉及两个小因子eIF 1和eIF 1A与小（40 S）核糖体亚基的结合。这有助于tRNA结合，允许扫描mRNA，并保持起始密码子识别的保真度。使用cryo-EM，我们已经获得了与OR和eIF 1A结合的40 S的3D重建，并且单独使用每种因子。这些结构表明，OR和eIF 1A一起稳定了打开mRNA结合通道的构象变化。生物化学数据显示，这两种因子均加速三元复合物（eIF 2.GTP.Met-tRNA（i）（Met））与40 S结合的速率，但只有eIF 1A稳定这种相互作用。我们的研究结果表明，eIF 1和eIF 1 A促进开放的，扫描能力的preinitiation复合物，关闭后，起始密码子识别和eIF 1释放，以稳定三元复合物结合和钳制mRNA。
Initiation of translation is the process by which initiator tRNA and the start codon of mRNA are positioned in the ribosomal P site. In eukaryotes, one of the first steps involves the binding of two small factors, eIF1 and eIF1A, to the small (40S) ribosomal subunit. This facilitates tRNA binding, allows scanning of mRNA, and maintains fidelity of start codon recognition. Using cryo-EM, we have obtained 3D reconstructions of 40S bound to both OR and eIF1 A, and with each factor alone. These structures reveal that together, OR and eIF1A stabilize a conformational change that opens the mRNA binding channel. Biochemical data reveal that both factors accelerate the rate of ternary complex (eIF2.GTP.Met-tRNA(i)(Met)) binding to 40S but only eIF1A stabilizes this interaction. Our results suggest that eIF1 and eIF1 A promote an open, scanning-competent preinitiation complex that closes upon start codon recognition and eIF1 release to stabilize ternary complex binding and clamp down on mRNA.