Institut für Medizinische Physik und Biophysik, Charité - Universitätsmedizin Berlin, Ziegelstrasse 5-9, 10117 Berlin, Germany.
Mol Cell. 2011 Oct 21;44(2):214-24. doi: 10.1016/j.molcel.2011.07.040.
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 pretranslocation complex reveal spontaneous, large-scale conformational changes, including an intersubunit 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 favored 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.
尽管核糖体的结构核心在所有生命领域中都是保守的，但真核核糖体比其细菌对应物大得多且复杂得多。这些差异在多大程度上影响翻译的分子机制仍不清楚。哺乳动物前移位复合物的多颗粒低温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，包括核糖体亚基之间的亚基间旋转。通过结构相关的过程，tRNA 底物在其 L 形折叠的局部变化的促进下在经典和至少两种不同的杂交构象之间振荡。杂种状态在哺乳动物复合物中更为有利。然而，通过 tRNA 与 E 位的结合或通过真核特异性抗生素和易位抑制剂环己酰亚胺，经典 tRNA 位置可以恢复。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区别，为不同的翻译调控策略和物种特异性抗生素作用提供了机制基础。
