Intrinsic disorder in transcription factors

被引:560
作者
Liu, Jiangang
Perumal, Narayanan B.
Oldfield, Christopher J.
Su, Eric W.
Uversky, Vladimir N.
Dunker, A. Keith
机构
[1] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA
[3] Indiana Univ Purdue Univ, Sch Informat, Indianapolis, IN 46202 USA
[4] Eli Lilly & Co, Lilly Res Labs, Bioinformat Grp, Greenfield, IN 46140 USA
[5] Russian Acad Sci, Inst Biol Instrument, Pushchino 142292, Moscow Region, Russia
[6] Mol Kinet Inc, Indianapolis, IN 46268 USA
关键词
D O I
10.1021/bi0602718
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Intrinsic disorder (ID) is highly abundant in eukaryotes, which reflect the greater need for disorder-associated signaling and transcriptional regulation in nucleated cells. Although several well-characterized examples of intrinsically disordered proteins in transcriptional regulation have been reported, no systematic analysis has been reported so far. To test for the general prevalence of intrinsic disorder in transcriptional regulation, we used the predictor of natural disorder regions (PONDR) to analyze the abundance of intrinsic disorder in three transcription factor datasets and two control sets. This analysis revealed that from 94.13 to 82.63% of transcription factors possess extended regions of intrinsic disorder, relative to 54.51 and 18.64% of the proteins in two control datasets, which indicates the significant prevalence of intrinsic disorder in transcription factors. This propensity of transcription factors to intrinsic disorder was confirmed by cumulative distribution function analysis and charge-hydropathy plots. The amino acid composition analysis showed that all three transcription factor datasets were substantially depleted in order-promoting residues and significantly enriched in disorder-promoting residues. Our analysis of the distribution of disorder within the transcription factor datasets revealed that (a) the AT-hooks and basic regions of transcription factor DNA-binding domains are highly disordered; (b) the degree of disorder in transcription factor activation regions is much higher than that in DNA-binding domains; (c) the degree of disorder is significantly higher in eukaryotic transcription factors than in prokaryotic transcription factors; and (d) the level of alpha-MoRF (molecular recognition feature) prediction is much higher in transcription factors. Overall, our data reflected the fact that eukaryotes with well-developed gene transcription machinery require transcription factor flexibility to be more efficient.
引用
收藏
页码:6873 / 6888
页数:16
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