Cotranslational Protein Folding and Terminus Hydrophobicity

[摘要] Peptides fold on a time scale that is much smaller than the time required for synthesis, whence all proteinspotentially fold cotranslationally to some degree (followed by additional folding events after release from theribosome). In this paper, in three different ways, we find that cotranslational folding success is associated withhigher hydrophobicity at the N-terminus than at the C-terminus. First, we fold simple HP models on a squarelattice and observe that HP sequences that fold better cotranslationally than from a fully extended state exhibita positive difference (N−C) in terminus hydrophobicity. Second, we examine real proteins using apreviously established measure of potential cotranslationality known as ALR (Average Logarithmic Ratio of theextent 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 tofolding is more successful for proteins with higher N-terminus than C-terminus hydrophobicity. All resultsindicate that cotranslational folding is promoted in part by a hydrophobic start and a less hydrophobic finish tothe sequence.

[学科分类] 生物技术