Structure and dynamics of the mammalian ribosomal pretranslocation complex.
Structure and dynamics of the mammalian ribosomal pretranslocation complex.
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DOI：
10.1016/j.molcel.2011.07.040
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发表时间：
2011-10-21
期刊：
影响因子：
16
通讯作者：
Spahn CM
中科院分区：
文献类型：
--
作者：
Budkevich T;Giesebrecht J;Altman RB;Munro JB;Mielke T;Nierhaus KH;Blanchard SC;Spahn CM
虽然核糖体的结构核心在所有生命王国中都是保守的，但真核细胞的核糖体比细菌核糖体要大得多，也更复杂。这些差异在多大程度上影响翻译的分子机制仍然是个未知数。哺乳动物预易位复合体的多粒子冷冻电子显微镜和单分子FRET研究揭示了自发的、大规模的构象变化，包括核糖体亚基的亚基间旋转。通过结构相关的过程，tRNA底物在经典的和至少两种不同的杂交构型之间振荡，这得益于其L形状折叠的局部化变化。在哺乳动物复合体中，杂交状态是受欢迎的。然而，经典的tRNA位置可以通过tRNA与E位结合或真核生物特异性抗生素和易位抑制剂放线菌亚胺来恢复。这些发现揭示了细菌和哺乳动物核糖体在结构和能量特征上的关键差异，为不同的翻译调控策略和物种特异性的抗生素作用提供了机制基础。
Although the structural core of the ribosome is conserved in all kingdoms of life, eukaryotic ribosomes are significantly larger and more complex than their bacterial counterparts. The extent to which these differences influence the molecular mechanism of translation remains elusive. Multiparticle cryo-electron microscopy and single-molecule FRET investigations of the mammalian pre-translocation complex reveal spontaneous, large-scale conformational changes including an inter-subunit rotation of the ribosomal subunits. Through structurally related processes, tRNA substrates oscillate between classical and at least two distinct hybrid configurations facilitated by localized changes in their L-shaped fold. Hybrid states are favoured within the mammalian complex. However, classical tRNA positions can be restored by tRNA binding to the E site or by the eukaryotic-specific antibiotic and translocation inhibitor, cycloheximide. These findings reveal critical distinctions in the structural and energetic features of bacterial and mammalian ribosomes, providing a mechanistic basis for divergent translation regulation strategies and species-specific antibiotic action.
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DOI：
10.1073/pnas.0805299105
发表时间：
2008-10-07
影响因子：
11.1
作者：
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影响因子：
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影响因子：
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DOI：
10.1126/science.1202692
发表时间：
2011-05-20
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
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影响因子：
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