In eukaryotic cells, the ubiquitin-proteasome system serves to remove proteins that are either dysfunctional or no longer needed. The 26S proteasome is a 2.5 MDa multisubunit complex comprising the 20S core particle, where degradation is executed, and one or two regulatory particles which prepare substrates for degradation. Whereas the 20S core particles of several species had been studied extensively by X-ray crystallography, the 26S holocomplex structure had remained elusive for a long time. Recent advances in single-particle cryo-electron microscopy have changed the situation and provided atomic resolution models of this intriguing molecular machine and its dynamics. Besides, cryo-electron tomography enables structural studies in situ, providing molecular resolution images of macromolecules inside pristinely preserved cellular environments. This has greatly contributed to our understanding of proteasome dynamics in the context of cells.

在真核细胞中，泛素-蛋白酶体系统用于去除功能障碍或不再需要的蛋白质。26S蛋白酶体是一个2.5 MDa多亚基复合物，包含20S核心颗粒（可进行降解）和一个或两个可调控降解底物的调节颗粒。X射线晶体学已对多种物种的20S核心颗粒进行了广泛研究，而26S全络合物结构长期以来仍难以捉摸。单粒子冷冻电子显微镜的最新进展改变了这种状况，并提供了这种有趣的分子机器及其动力学的原子分辨率模型。此外，低温电子断层扫描可以进行原位结构研究，提供原始保存的细胞环境中大分子的分子分辨率图像。这极大地促进了我们对细胞中蛋白酶体动力学的理解。