Cotranslational protein folding on the ribosome monitored in real time
Cotranslational protein folding on the ribosome monitored in real time
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DOI：
10.1126/science.aad0344
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发表时间：
2015-11-27
期刊：
影响因子：
56.9
通讯作者：
Rodnina, Marina V.
中科院分区：
文献类型：
--
作者：
Holtkamp, Wolf;Kokic, Goran;Rodnina, Marina V.
当蛋白质结构域在核糖体上合成时，它们可以折叠成稳定的三级结构。我们使用一个高效的、重组的体外翻译系统，实时研究了一个小的五螺旋蛋白结构域--大肠杆菌N5-谷氨酰胺甲基转移酶HEMK的N-末端结构域的折叠。我们的观察表明，蛋白质的共翻译折叠在溶液中自动快速折叠，通过在核糖体的多肽隧道内形成的紧凑的非天然构象进行。在核糖体出现完整结构域序列后，紧凑状态立即重排成类天然结构。这两种折叠转变都受到平移的速率限制，允许对核糖体限制的构象空间进行准平衡采样。共翻译折叠可能是典型的小的、本质上快速折叠的蛋白质结构域。
Protein domains can fold into stable tertiary structures while they are synthesized on the ribosome. We used a high-performance, reconstituted in vitro translation system to investigate the folding of a small five-helix protein domain-the N-terminal domain of Escherichia coli N5-glutamine methyltransferase HemK-in real time. Our observations show that cotranslational folding of the protein, which folds autonomously and rapidly in solution, proceeds through a compact, non-native conformation that forms within the peptide tunnel of the ribosome. The compact state rearranges into a native-like structure immediately after the full domain sequence has emerged from the ribosome. Both folding transitions are rate-limited by translation, allowing for quasi-equilibrium sampling of the conformational space restricted by the ribosome. Cotranslational folding may be typical of small, intrinsically rapidly folding protein domains.