Accuracy mechanism of eukaryotic ribosome translocation.
Accuracy mechanism of eukaryotic ribosome translocation.
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DOI：
10.1038/s41586-021-04131-9
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发表时间：
2021-12
期刊：
影响因子：
64.8
通讯作者：
Yusupova G
中科院分区：
文献类型：
--
作者：
Djumagulov M;Demeshkina N;Jenner L;Rozov A;Yusupov M;Yusupova G
遗传密码向蛋白质的翻译是通过信使RNA（mRNA）和转运RNA（tRNA）通过核糖体的重复同步易位来实现的。在真核生物中，易位由延伸因子2（eEF 2）确保，其催化该过程并积极地有助于其准确性。虽然许多研究指出，eEF 2和tRNA修饰中的保守真核生物翻译后修饰diphthamide在支持易位的准确性方面起着关键作用，但描述其特定功能的详细分子机制仍知之甚少。在这里，我们报告了一个高分辨率的X射线结构的真核80 S核糖体的易位中间状态含有mRNA，天然修饰的eEF 2和tRNA。晶体结构揭示了密码子-反密码子相互作用的稳定网络，涉及苯丙氨酸tRNA的第37位的二苯二甲酰胺和高度修饰的核苷间布胞嘧啶，这也是已知的，以提高翻译的准确性。该模型演示了解码中心如何释放密码子-反密码子双链体，允许其在核糖体上移动，并强调eEF 2作为定义易位方向性的“棘爪”的功能。该模型表明80 S核糖体、eEF 2和tRNA的真核生物特异性元件如何进行大规模分子重组，以确保在复杂的易位过程中维持mRNA阅读框架。被困在一个中间易位状态的酿酒酵母80 S核糖体的结构分析显示稳定的密码子-反密码子相互作用的真核生物特异性元件的80 S核糖体，eEF 2和tRNA，并证明了一个主要的作用eEF 2在维持易位的方向性。
Translation of the genetic code into proteins is realized through repetitions of synchronous translocation of messenger RNA (mRNA) and transfer RNAs (tRNA) through the ribosome. In eukaryotes translocation is ensured by elongation factor 2 (eEF2), which catalyses the process and actively contributes to its accuracy. Although numerous studies point to critical roles for both the conserved eukaryotic posttranslational modification diphthamide in eEF2 and tRNA modifications in supporting the accuracy of translocation, detailed molecular mechanisms describing their specific functions are poorly understood. Here we report a high-resolution X-ray structure of the eukaryotic 80S ribosome in a translocation-intermediate state containing mRNA, naturally modified eEF2 and tRNAs. The crystal structure reveals a network of stabilization of codon–anticodon interactions involving diphthamide and the hypermodified nucleoside wybutosine at position 37 of phenylalanine tRNA, which is also known to enhance translation accuracy. The model demonstrates how the decoding centre releases a codon–anticodon duplex, allowing its movement on the ribosome, and emphasizes the function of eEF2 as a ‘pawl’ defining the directionality of translocation. This model suggests how eukaryote-specific elements of the 80S ribosome, eEF2 and tRNAs undergo large-scale molecular reorganizations to ensure maintenance of the mRNA reading frame during the complex process of translocation. Structural analysis of the Saccharomyces cerevisiae 80S ribosome trapped in an intermediate translocation state shows stabilization of codon–anticodon interactions by eukaryote-specific elements of the 80S ribosome, eEF2 and tRNA and demonstrates a major role for eEF2 in maintaining the directionality of translocation.
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影响因子：
5.6
作者：
Peske, F;Savelsbergh, A;Wintermeyer, W
通讯作者：
Wintermeyer, W
影响因子：
56.9
作者：
Ogle, JM;Brodersen, DE;Ramakrishnan, V
通讯作者：
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影响因子：
11.4
作者：
Spahn, CMT;Gomez-Lorenzo, MG;Frank, J
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Frank, J
FEM：功能增强的地图。
DOI：
10.1107/s1399004714028132
发表时间：
2015-03
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Afonine PV;Moriarty NW;Mustyakimov M;Sobolev OV;Terwilliger TC;Turk D;Urzhumtsev A;Adams PD
通讯作者：
Adams PD
影响因子：
8.8
作者：
Flis, Julia;Holm, Mikael;Budkevich, Tatyana V.
通讯作者：
Budkevich, Tatyana V.