Structural insights on the dynamics of proteasome formation.
Structural insights on the dynamics of proteasome formation.
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DOI：
10.1007/s12551-017-0381-4
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发表时间：
2018-04-01
影响因子：
--
通讯作者：
Satoh, Tadashi
中科院分区：
文献类型：
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作者：
Kato, Koichi;Satoh, Tadashi
生物系统中的分子组织包括涉及生物分子亚稳态复合物形成的精心编程的过程。蛋白酶体是最大和最复杂的生物超分子复合物之一。这种生物分子机制包括大约70个亚基，包括结构上同源但功能上不同的亚基，从而发挥多功能蛋白水解功能。在真核生物中，蛋白酶体的形成是非自主的，并由装配分子伴侣辅助，其与装配中间体瞬时结合，作为分子匹配器和蛋白酶体亚基正确装配的检查点。积累的数据也表明，真核生物蛋白酶体的形成涉及报废和建设机制。然而，与真核生物蛋白酶体亚基不同，古细菌亚基几乎没有结构差异，并自发组装成功能机器。然而，古细菌基因组编码真核生物蛋白酶体组装分子伴侣的同源物。最近对这些蛋白质的结构和功能的研究已经推进了我们对蛋白酶体生物合成中分子机制进化的理解。这些知识，反过来，提供了一个指导原则，在设计分子机器使用蛋白质工程方法和从头合成的人工分子系统。
Molecular organization in biological systems comprises elaborately programmed processes involving metastable complex formation of biomolecules. This is exemplified by the formation of the proteasome, which is one of the largest and most complicated biological supramolecular complexes. This biomolecular machinery comprises approximately 70 subunits, including structurally homologous, but functionally distinct, ones, thereby exerting versatile proteolytic functions. In eukaryotes, proteasome formation is non-autonomous and is assisted by assembly chaperones, which transiently associate with assembly intermediates, operating as molecular matchmakers and checkpoints for the correct assembly of proteasome subunits. Accumulated data also suggest that eukaryotic proteasome formation involves scrap-and-build mechanisms. However, unlike the eukaryotic proteasome subunits, the archaeal subunits show little structural divergence and spontaneously assemble into functional machinery. Nevertheless, the archaeal genomes encode homologs of eukaryotic proteasome assembly chaperones. Recent structural and functional studies of these proteins have advanced our understanding of the evolution of molecular mechanisms involved in proteasome biogenesis. This knowledge, in turn, provides a guiding principle in designing molecular machineries using protein engineering approaches and de novo synthesis of artificial molecular systems.