文献类型：期刊文献

英文题名：Nonoptimal codon usage influences protein structure in intrinsically disordered regions

作者：Zhou, Mian[1,3];Wang, Tao[2];Fu, Jingjing[1];Xiao, Guanghua[2];Liu, Yi[1]

机构：[1]Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA;[2]Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA;[3]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2015

卷号：97

期号：5

起止页码：974

外文期刊名：MOLECULAR MICROBIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000360098600013)】；

基金：We thank Haiyan Yuan for technical assistance, and Drs. Nick Grishin and Keith Dunker for their helpful suggestions. This work was supported by grants from the National Institutes of Health to Y. Liu (GM068496 and GM062591) and G. Xiao (R01CA172211), and from the Welch Foundation (I-1560) to Y. Liu.

语种：英文

摘要：Synonymous codons are not used with equal frequencies in most genomes. Codon usage has been proposed to play a role in regulating translation kinetics and co-translational protein folding. The relationship between codon usage and protein structures and the in vivo role of codon usage in eukaryotic protein folding is not clear. Here, we show that there is a strong codon usage bias in the filamentous fungus Neurospora. Importantly, we found genome-wide correlations between codon choices and predicted protein secondary structures: Nonoptimal codons are preferentially used in intrinsically disordered regions, and more optimal codons are used in structured domains. The functional importance of such correlations in vivo was confirmed by structure-based codon manipulation of codons in the Neurospora circadian clock gene frequency (frq). The codon optimization of the predicted disordered, but not well-structured regions of FRQ impairs clock function and altered FRQ structures. Furthermore, the correlations between codon usage and protein disorder tendency are conserved in other eukaryotes. Together, these results suggest that codon choices and protein structures co-evolve to ensure proper protein folding in eukaryotic organisms.