Describing sequence-ensemble relationships for intrinsically disordered proteins

Biochem J. 2013 Jan 15;449(2):307-18. doi: 10.1042/BJ20121346.

Abstract

Intrinsically disordered proteins participate in important protein-protein and protein-nucleic acid interactions and control cellular phenotypes through their prominence as dynamic organizers of transcriptional, post-transcriptional and signalling networks. These proteins challenge the tenets of the structure-function paradigm and their functional mechanisms remain a mystery given that they fail to fold autonomously into specific structures. Solving this mystery requires a first principles understanding of the quantitative relationships between information encoded in the sequences of disordered proteins and the ensemble of conformations they sample. Advances in quantifying sequence-ensemble relationships have been facilitated through a four-way synergy between bioinformatics, biophysical experiments, computer simulations and polymer physics theories. In the present review we evaluate these advances and the resultant insights that allow us to develop a concise quantitative framework for describing the sequence-ensemble relationships of intrinsically disordered proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Binding Sites
  • Models, Molecular
  • Peptides / chemistry
  • Protein Binding
  • Protein Conformation*
  • Protein Folding*
  • Protein Structure, Tertiary*
  • Proteins / chemistry*
  • Solvents / chemistry
  • Thermodynamics

Substances

  • Peptides
  • Proteins
  • Solvents
  • polyglutamine