Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA.
Biomolecules. 2023 Aug 6;13(8):1223. doi: 10.3390/biom13081223.
The 26S proteasome is the largest and most complicated protease known, and changes to proteasome assembly or function contribute to numerous human diseases. Assembly of the 26S proteasome from its ~66 individual polypeptide subunits is a highly orchestrated process requiring the concerted actions of both intrinsic elements of proteasome subunits, as well as assistance by extrinsic, dedicated proteasome assembly chaperones. With the advent of near-atomic resolution cryo-electron microscopy, it has become evident that the proteasome is a highly dynamic machine, undergoing numerous conformational changes in response to ligand binding and during the proteolytic cycle. In contrast, an appreciation of the role of conformational dynamics during the biogenesis of the proteasome has only recently begun to emerge. Herein, we review our current knowledge of proteasome assembly, with a particular focus on how conformational dynamics guide particular proteasome biogenesis events. Furthermore, we highlight key emerging questions in this rapidly expanding area.
26S 蛋白酶体是已知最大、最复杂的蛋白酶，其组装或功能的改变与许多人类疾病有关。由大约 66 个单独多肽亚基组成的 26S 蛋白酶体的组装是一个高度协调的过程，需要蛋白酶体亚基的内在元件的协同作用，以及由外在的、专门的蛋白酶体组装伴侣的辅助。随着近原子分辨率冷冻电子显微镜的出现，很明显，蛋白酶体是一个高度动态的机器，在配体结合和在蛋白水解循环期间会发生许多构象变化。相比之下，最近才开始认识到构象动力学在蛋白酶体生物发生过程中的作用。本文综述了我们目前对蛋白酶体组装的认识，特别关注构象动力学如何指导特定的蛋白酶体生物发生事件。此外，我们还强调了这个快速发展领域中的关键新问题。
