Prediction of variable translation rate effects on cotranslational protein folding
Prediction of variable translation rate effects on cotranslational protein folding
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DOI：
10.1038/ncomms1850
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发表时间：
2012-05-01
影响因子：
16.6
通讯作者：
Dobson, Christopher M.
中科院分区：
文献类型：
--
作者：
O'Brien, Edward P.;Vendruscolo, Michele;Dobson, Christopher M.
蛋白质的折叠及其在核糖体上的合成受到许多不同时间尺度的影响，包括翻译速率。在这里，我们提出了一个动力学的形式主义来描述共翻译折叠和预测可变的翻译速率对这个过程的影响。我们的方法，它利用被捕的核糖体新生链复合物的平衡数据，提供结构域折叠概率在定量协议与分子模拟折叠在不同的翻译速率。我们表明，信使RNA中的单密码子突变改变翻译速率的影响，可以导致在特定条件下折叠程度的显着增加。我们讨论的动力学形式主义可以描述发生在单个核糖体分子上的共翻译折叠过程，也可以描述一组随机翻译核糖体的共翻译折叠过程。
The concomitant folding of a protein with its synthesis on the ribosome is influenced by a number of different timescales including the translation rate. Here we present a kinetic formalism to describe cotranslational folding and predict the effects of variable translation rates on this process. Our approach, which utilizes equilibrium data from arrested ribosome nascent chain complexes, provides domain folding probabilities in quantitative agreement with molecular simulations of folding at different translation rates. We show that the effects of single codon mutations in messenger RNA that alter the translation rate can lead to a dramatic increase in the extent of folding under specific conditions. The kinetic formalism that we discuss can describe the cotranslational folding process occurring on a single ribosome molecule as well as for a collection of stochastically translating ribosomes.