Calmodulin signaling

Analysis and prediction of a disorder-dependent molecular recognition

Predrag Radivojac, Slobodan Vucetic, Timothy R. O'Connor, Vladimir N. Uversky, Zoran Obradovic, A. Dunker

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Calmodulin (CaM) signaling involves important, wide spread eukaryotic protein-protein interactions. The solved structures of CaM associated with several of its binding targets, the distinctive binding mechanism of CaM, and the significant trypsin sensitivity of the binding targets combine to indicate that the process of association likely involves coupled binding and folding for both CaM and its binding targets. Here, we use bioinformatics approaches to test the hypothesis that CaM-binding targets are intrinsically disordered. We developed a predictor of CaM-binding regions and estimated its performance. Per residue accuracy of this predictor reached 81%, which, in combination with a high recall/precision balance at the binding region level, suggests high predictability of CaM-binding partners. An analysis of putative CaM-binding proteins in yeast and human strongly indicates that their molecular functions are related to those of intrinsically disordered proteins. These findings add to the growing list of examples in which intrinsically disordered protein regions are indicated to provide the basis for cell signaling and regulation.

Original languageEnglish
Pages (from-to)398-410
Number of pages13
JournalProteins: Structure, Function and Genetics
Volume63
Issue number2
DOIs
StatePublished - May 1 2006

Fingerprint

Molecular recognition
Calmodulin
Intrinsically Disordered Proteins
Cell signaling
Calmodulin-Binding Proteins
Bioinformatics
Computational Biology
Yeast
Trypsin
Proteins
Yeasts
Association reactions

Keywords

  • Protein function
  • Protein-protein interactions
  • Unfolded
  • Unstructured

ASJC Scopus subject areas

  • Genetics
  • Structural Biology
  • Biochemistry

Cite this

Calmodulin signaling : Analysis and prediction of a disorder-dependent molecular recognition. / Radivojac, Predrag; Vucetic, Slobodan; O'Connor, Timothy R.; Uversky, Vladimir N.; Obradovic, Zoran; Dunker, A.

In: Proteins: Structure, Function and Genetics, Vol. 63, No. 2, 01.05.2006, p. 398-410.

Research output: Contribution to journalArticle

Radivojac, Predrag ; Vucetic, Slobodan ; O'Connor, Timothy R. ; Uversky, Vladimir N. ; Obradovic, Zoran ; Dunker, A. / Calmodulin signaling : Analysis and prediction of a disorder-dependent molecular recognition. In: Proteins: Structure, Function and Genetics. 2006 ; Vol. 63, No. 2. pp. 398-410.
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