1] Centre for Integrative Biology (CBI), Department of Integrated Structural Biology, IGBMC (Institute of Genetics and of Molecular and Cellular Biology), 1 rue Laurent Fries, 67404 Illkirch, France [2] Centre National de la Recherche Scientifique (CNRS), UMR 7104, 67404 Illkirch, France [3] Institut National de la Santé et de la Recherche Médicale (INSERM) U964, 67404 Illkirch, France [4] Université de Strasbourg, 67081 Strasbourg, France.
Nature. 2015 Apr 30;520(7549):640-5. doi: 10.1038/nature14427. Epub 2015 Apr 22.
Ribosomes are translational machineries that catalyse protein synthesis. Ribosome structures from various species are known at the atomic level, but obtaining the structure of the human ribosome has remained a challenge; efforts to address this would be highly relevant with regard to human diseases. Here we report the near-atomic structure of the human ribosome derived from high-resolution single-particle cryo-electron microscopy and atomic model building. The structure has an average resolution of 3.6 Å, reaching 2.9 Å resolution in the most stable regions. It provides unprecedented insights into ribosomal RNA entities and amino acid side chains, notably of the transfer RNA binding sites and specific molecular interactions with the exit site tRNA. It reveals atomic details of the subunit interface, which is seen to remodel strongly upon rotational movements of the ribosomal subunits. Furthermore, the structure paves the way for analysing antibiotic side effects and diseases associated with deregulated protein synthesis.
核糖体是催化蛋白质合成的翻译机器。各种物种的核糖体结构已在原子水平上为人所知,但获得人类核糖体的结构仍然是一个挑战;解决这一问题的努力将与人类疾病高度相关。在这里,我们报道了通过高分辨率单颗粒冷冻电子显微镜和原子模型构建获得的人类核糖体的近原子结构。该结构的平均分辨率为 3.6Å,在最稳定的区域达到 2.9Å 的分辨率。它为核糖体 RNA 实体和氨基酸侧链提供了前所未有的见解,特别是转移 RNA 结合位点和与出口 tRNA 的特定分子相互作用。它揭示了亚基接口的原子细节,该接口在核糖体亚基的旋转运动中被强烈重塑。此外,该结构为分析抗生素副作用和与蛋白质合成失调相关的疾病铺平了道路。