Department of Molecular Biosciences, Kyoto Sangyo University Kamigamo-Motoyama, Kita-ku, Kyoto, Japan.
Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, Japan.
J Biochem. 2018 Nov 1;164(5):369-379. doi: 10.1093/jb/mvy061.
Chaperonins assist folding of many cellular proteins, including essential proteins for cell viability. However, it remains unclear how chaperonin-assisted folding is different from spontaneous folding. Chaperonin GroEL/GroES facilitates folding of denatured protein encapsulated in its central cage but the denatured protein often escapes from the cage to the outside during reaction. Here, we show evidence that the in-cage-folding and the escape occur diverging from the same intermediate complex in which polypeptide is tethered loosely to the cage and partly protrudes out of the cage. Furthermore, denatured proteins in the chaperonin cage are kept in more extended conformation than those initially formed in spontaneous folding. We propose that the formation of tethered intermediate of polypeptide is necessary to prevent polypeptide collapse at the expense of polypeptide escape. The tethering of polypeptide would allow freely mobile portions of tethered polypeptide to fold segmentally.
伴侣蛋白协助许多细胞蛋白的折叠，包括对细胞存活至关重要的蛋白。然而，伴侣蛋白协助折叠与自发折叠的区别仍不清楚。GroEL/GroES 伴侣蛋白促进包埋在其中央笼内的变性蛋白的折叠，但在反应过程中，变性蛋白经常从笼内逃逸到笼外。在这里，我们提供的证据表明，笼内折叠和逃逸是从同一个中间复合物中发散出来的，在这个复合物中，多肽松散地连接到笼上，并部分从笼中伸出。此外，笼内伴侣蛋白中的变性蛋白保持在比自发折叠中最初形成的更伸展的构象。我们提出，形成多肽的束缚中间物对于防止多肽折叠而不是多肽逃逸是必要的。多肽的束缚允许束缚多肽的自由移动部分分段折叠。
