Knot formation in newly translated proteins is spontaneous and accelerated by chaperonins
Knot formation in newly translated proteins is spontaneous and accelerated by chaperonins
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DOI：
10.1038/nchembio.742
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发表时间：
2012-02-01
影响因子：
14.8
通讯作者：
Jackson, Sophie E.
中科院分区：
文献类型：
--
作者：
Mallam, Anna L.;Jackson, Sophie E.
拓扑结在相当数量的蛋白质结构中被发现，但尚不清楚它们在细胞环境中如何打结和折叠。我们研究了打结的蛋白质分子的行为，因为它们是第一次合成的核糖体使用无细胞翻译系统。我们发现，新翻译的打结蛋白可以自发地自我捆绑，不需要分子伴侣的协助下正确折叠到其三叶结结构。这个过程缓慢但有效，我们没有发现错误折叠物种的证据。动力学分析表明，打结过程是速率限制性的，发生在发病后，并且由GroEL-GroES伴侣蛋白复合物特异性地和显著地（P < 0.001）加速。这表明了一种新的活性机制，这种分子伴侣，并表明伴侣蛋白催化打结可能占主导地位，在体内。这些结果解释了打结的蛋白质结构是如何经受住进化压力的，尽管它们的拓扑结构很复杂。
Topological knots are found in a considerable number of protein structures, but it is not clear how they knot and fold within the cellular environment. We investigated the behavior of knotted protein molecules as they are first synthesized by the ribosome using a cell-free translation system. We found that newly translated knotted proteins can spontaneously self-tie and do not require the assistance of molecular chaperones to fold correctly to their trefoil-knotted structures. This process is slow but efficient, and we found no evidence of misfolded species. A kinetic analysis indicates that the knotting process is rate limiting, occurs post-translationally, and is specifically and significantly (P < 0.001) accelerated by the GroEL-GroES chaperonin complex. This demonstrates a new active mechanism for this molecular chaperone and suggests that chaperonin-catalyzed knotting probably dominates in vivo. These results explain how knotted protein structures have withstood evolutionary pressures despite their topological complexity.