Structural snapshots of actively translating human ribosomes.
Structural snapshots of actively translating human ribosomes.
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DOI：
10.1016/j.cell.2015.03.052
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发表时间：
2015-05-07
期刊：
影响因子：
64.5
通讯作者：
Spahn CM
中科院分区：
文献类型：
--
作者：
Behrmann E;Loerke J;Budkevich TV;Yamamoto K;Schmidt A;Penczek PA;Vos MR;Bürger J;Mielke T;Scheerer P;Spahn CM
大分子机器，如核糖体，在其功能周期中经历大规模的构象变化。虽然它们的作用模式经常被比作机械机器，但一个关键的区别是，在分子尺度上，热力学效应主导着功能循环，蛋白质在能量景观上的能量最小值所定义的功能状态之间随机波动。在这里，我们已经使用冷冻电子显微镜成像离体衍生的人类多聚核糖体作为积极翻译核糖体的来源。多粒子细化和三维变异性分析使我们能够可视化各种各样的本地翻译中间体。显著填充的状态不仅包括在前和后易位状态中的延伸循环中间体，而且还包括含有eEF 1A的解码和终止/再循环复合物。专注于易位后的状态，我们将这种评估扩展到单残基水平，揭示了核糖体-配体相互作用的惊人细节，并确定了静态和功能上重要的动态元素。
Macromolecular machines, such as the ribosome, undergo large-scale conformational changes during their functional cycles. While their mode of action is often compared to that of mechanical machines, a crucial difference is that at the molecular dimension, thermodynamic effects dominate functional cycles, with proteins fluctuating stochastically between functional states defined by energetic minima on an energy landscape. Here, we have used cryo-electron microscopy to image ex vivo-derived human polysomes as a source of actively translating ribosomes. Multiparticle refinement and three-dimensional variability analysis allowed us to visualize a variety of native translation intermediates. Significantly populated states include not only elongation cycle intermediates in pre- and post-translocational states, but also eEF1A-containing decoding and termination/recycling complexes. Focusing on the post-translocational state, we extended this assessment to the single-residue level, uncovering striking details of ribosome-ligand interactions and identifying both static and functionally important dynamic elements.
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