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PMID: 16734424 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Intrinsic disorder in transcription factors.

Biochemistry ·Vol. 45 ·No. 22 ·2006-06-06 ·Pages 6873-88

Liu J, Perumal NB, Oldfield CJ, Su EW, Uversky VN, Dunker AK

Abstract

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.

MeSH Terms
Amino Acid Sequence Databases, Protein Humans Molecular Sequence Data Protein Conformation Protein Structure, Tertiary Transcription Factors/chemistry,physiology
Chemicals
Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Liu Jiangang
School of Informatics, Indiana University-Purdue University Indianapolis, 535 West Michigan Street, Indianapolis, Indiana 46202, USA.
Perumal Narayanan B
Oldfield Christopher J
Su Eric W
Uversky Vladimir N
Dunker A Keith
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Article Info
Journal
Biochemistry
Abbr.
Biochemistry
ISSN
0006-2960
DOI
10.1021/bi0602718
Published
2006-06-06
Pages
6873-88
Language
English
Region
United States
NLM ID
0370623
PMCID
PMC2538555
Subset
IM
Grants
NLM NIH HHS · R01 LM007688 · United States
NLM NIH HHS · R01 LM007688-01A1 · United States
External Links
PubMed source DOI: 10.1021/bi0602718 PMC Full Text View journal details
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