Unfoldomics of human genetic diseases: Illustrative examples of ordered and intrinsically disordered members of the human diseasome

Uros Midic, Christopher J. Oldfield, A. Keith Dunker, Zoran Obradovic, Vladimir N. Uversky

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Intrinsically disordered proteins (IDPs) constitute a recently recognized realm of atypical biologically active proteins that lack stable structure under physiological conditions, but are commonly involved in such crucial cellular processes as regulation, recognition, signaling and control. IDPs are very common among proteins associated with various diseases. Recently, we performed a systematic bioinformatics analysis of the human diseasome, a network that linked the human disease phenome (which includes all the human genetic diseases) with the human disease genome (which contains all the disease-related genes) (Goh, K. I., Cusick, M. E., Valle, D., Childs, B., Vidal, M., and Barabasi, A. L. (2007). The human disease network. Proc. Natl. Acad. Sci. U.S.A. 104, 8685-90). The analysis of this diseasome revealed that IDPs are abundant in proteins linked to human genetic diseases, and that different genetic disease classes varied dramatically in the IDP content (Midic U., Oldfield C.J., Dunker A.K., Obradovic Z., Uversky V.N. (2009) Protein disorder in the human diseasome: Unfoldomics of human genetic diseases. BMC Genomics. In press). Furthermore, many of the genetic diseaserelated proteins were shown to contain at least one molecular recognition feature, which is a relatively short loosely structured protein region within a mostly disordered segment with the feature gaining structure upon binding to a partner. Finally, alternative splicing was shown to be abundant among the diseasome genes. Based on these observations the humangenetic-disease-associated unfoldome was created. This minireview describes several illustrative examples of ordered and intrinsically disordered members of the human diseasome.

Original languageEnglish (US)
Pages (from-to)1533-1547
Number of pages15
JournalProtein and Peptide Letters
Volume16
Issue number12
DOIs
StatePublished - Dec 1 2009

Keywords

  • Diseasome
  • Genetic disease
  • Intrinsic disorder
  • Unfoldome

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology

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