Srivastava Sheenal, Patton Yumi, Fisher David W, Wood Graham R
Department of Statistics, Macquarie University, Sydney, NSW 2109, Australia.
Adv Bioinformatics. 2011;2011:176813. doi: 10.1155/2011/176813. Epub 2011 Jun 6.
Peptides fold on a time scale that is much smaller than the time required for synthesis, whence all proteins potentially fold cotranslationally to some degree (followed by additional folding events after release from the ribosome). In this paper, in three different ways, we find that cotranslational folding success is associated with higher hydrophobicity at the N-terminus than at the C-terminus. First, we fold simple HP models on a square lattice and observe that HP sequences that fold better cotranslationally than from a fully extended state exhibit a positive difference (N-C) in terminus hydrophobicity. Second, we examine real proteins using a previously established measure of potential cotranslationality known as ALR (Average Logarithmic Ratio of the extent of previous contacts) and again find a correlation with the difference in terminus hydrophobicity. Finally, we use the cotranslational protein structure prediction program SAINT and again find that such an approach to folding is more successful for proteins with higher N-terminus than C-terminus hydrophobicity. All results indicate that cotranslational folding is promoted in part by a hydrophobic start and a less hydrophobic finish to the sequence.
肽链折叠的时间尺度远小于合成所需的时间，因此所有蛋白质都有可能在一定程度上进行共翻译折叠（从核糖体释放后还会有额外的折叠事件）。在本文中，我们通过三种不同的方式发现，共翻译折叠的成功与N端的疏水性高于C端有关。首先，我们在正方晶格上折叠简单的HP模型，观察到与从完全伸展状态折叠相比，共翻译折叠效果更好的HP序列在末端疏水性上呈现正差值（N - C）。其次，我们使用先前建立的一种称为ALR（先前接触程度的平均对数比）的潜在共翻译性测量方法来研究真实蛋白质，再次发现与末端疏水性差异存在相关性。最后，我们使用共翻译蛋白质结构预测程序SAINT，同样发现对于N端疏水性高于C端的蛋白质，这种折叠方式更成功。所有结果表明，共翻译折叠部分是由序列中疏水的起始和疏水性较低的结尾所促进的。
