Transient Tertiary Structure Formation within the Ribosome Exit Port
Transient Tertiary Structure Formation within the Ribosome Exit Port
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DOI：
10.1021/ja106530y
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发表时间：
2010-12-01
影响因子：
15
通讯作者：
Dobson, Christopher M.
中科院分区：
文献类型：
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作者：
O'Brien, Edward P.;Hsu, Shang-Te Danny;Dobson, Christopher M.
核糖体的出口通道通常被认为足够窄，只有当新生链的特定片段完全从通道中挤出时，共翻译折叠才能开始。在分子模拟和实验对比的基础上，我们表明，当到达出口隧道的最后20埃时，新生链内可以形成启动蛋白质折叠所必需的远程接触。我们进一步表明，在这个“出口端口”中，大量的原生和非原生三级结构可以在不与核糖体本身空间重叠的情况下形成，并提供了一个我们的模拟预测可以在出口隧道中形成的结构元件库，并且可以进行实验测试。我们的研究结果表明，这些褶皱的三级结构元素只是暂时形成的，并且在隧道内外边界区域的稳定中点上。这些发现为解释最近一系列核糖体新生链复合物的实验研究和理解共翻译折叠本质的关键方面提供了一个框架。
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 angstrom 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.