Department of Chemistry, Lensfield Road, University of Cambridge, UK.
J Am Chem Soc. 2010 Dec 1;132(47):16928-37. doi: 10.1021/ja106530y. Epub 2010 Nov 9.
The exit tunnel of the ribosome is commonly considered to be sufficiently narrow that co-translational folding can begin only when specific segments of nascent chains are fully extruded from the tunnel. Here we show, on the basis of molecular simulations and comparison with experiment, that the long-range contacts essential for initiating protein folding can form within a nascent chain when it reaches the last 20 Å of the exit tunnel. We further show that, in this "exit port", a significant proportion of native and non-native tertiary structure can form without steric overlap with the ribosome itself, and provide a library of structural elements that our simulations predict can form in the exit tunnel and is amenable to experimental testing. Our results show that these elements of folded tertiary structure form only transiently and are at their midpoints of stability at the boundary region between the inside and the outside of the tunnel. These findings provide a framework for interpreting a range of recent experimental studies of ribosome nascent chain complexes and for understanding key aspects of the nature of co-translational folding.
核糖体的出口隧道通常被认为足够狭窄，以至于只有当新生链的特定片段完全从隧道中伸出时，共翻译折叠才能开始。在这里，我们基于分子模拟并与实验进行比较表明，对于起始蛋白质折叠至关重要的远程接触可以在新生链到达出口隧道的最后 20Å 时形成。我们进一步表明，在这个“出口口”中，在与核糖体本身没有空间重叠的情况下，可以形成大量的天然和非天然三级结构，并且提供了一个结构元素库，我们的模拟预测这些结构元素可以在出口隧道中形成，并且可以进行实验测试。我们的研究结果表明，这些折叠的三级结构的元素仅短暂形成，并且在隧道内部和外部之间的边界区域处于它们的中点稳定性。这些发现为解释一系列最近的核糖体新生链复合物的实验研究以及理解共翻译折叠的本质的关键方面提供了框架。
