Lopez Tom, Dalton Kevin, Frydman Judith
Department of Biology, Stanford University, Stanford, CA 94305, USA.
Biophysics Program, Stanford University, Stanford, CA 94305, USA.
J Mol Biol. 2015 Sep 11;427(18):2919-30. doi: 10.1016/j.jmb.2015.04.013. Epub 2015 Apr 30.
Protein folding in the cell requires the assistance of enzymes collectively called chaperones. Among these, the chaperonins are 1-MDa ring-shaped oligomeric complexes that bind unfolded polypeptides and promote their folding within an isolated chamber in an ATP-dependent manner. Group II chaperonins, found in archaea and eukaryotes, contain a built-in lid that opens and closes over the central chamber. In eukaryotes, the chaperonin TRiC/CCT is hetero-oligomeric, consisting of two stacked rings of eight paralogous subunits each. TRiC facilitates folding of approximately 10% of the eukaryotic proteome, including many cytoskeletal components and cell cycle regulators. Folding of many cellular substrates of TRiC cannot be assisted by any other chaperone. A complete structural and mechanistic understanding of this highly conserved and essential chaperonin remains elusive. However, recent work is beginning to shed light on key aspects of chaperonin function and how their unique properties underlie their contribution to maintaining cellular proteostasis.
细胞中的蛋白质折叠需要一类统称为伴侣蛋白的酶的协助。其中，伴侣素是1兆道尔顿的环状寡聚复合物，它结合未折叠的多肽，并以ATP依赖的方式在一个隔离的腔室内促进其折叠。在古细菌和真核生物中发现的II型伴侣素含有一个内置的盖子，该盖子在中央腔室上打开和关闭。在真核生物中，伴侣素TRiC/CCT是异源寡聚体，由两个堆叠的环组成，每个环有八个同源亚基。TRiC促进了大约10%的真核蛋白质组的折叠，包括许多细胞骨架成分和细胞周期调节因子。TRiC的许多细胞底物的折叠不能由任何其他伴侣蛋白协助。对这种高度保守且必不可少的伴侣素的完整结构和机制理解仍然难以捉摸。然而，最近的研究开始揭示伴侣素功能的关键方面，以及它们的独特特性如何构成其对维持细胞蛋白质稳态的贡献的基础。
