Quantitative biophysical characterization of intrinsically disordered proteins

Eric B. Gibbs, Scott A. Showalter

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Intrinsically disordered proteins (IDPs) are broadly defined as protein regions that do not cooperatively fold into a spatially or temporally stable structure. Recent research strongly supports the hypothesis that a conserved functional role for structural disorder renders IDPs uniquely capable of functioning in biological processes such as cellular signaling and transcription. Recently, the frequency of application of rigorous mechanistic biochemistry and quantitative biophysics to disordered systems has increased dramatically. For example, the launch of the Protein Ensemble Database (pE-DB) demonstrates that the potential now exists to refine models for the native state structure of IDPs using experimental data. However, rigorous assessment of which observables place the strongest and least biased constraints on those ensembles is now needed. Most importantly, the past few years have seen strong growth in the number of biochemical and biophysical studies attempting to connect structural disorder with function. From the perspective of equilibrium thermodynamics, there is a clear need to assess the relative significance of hydrophobic versus electrostatic forces in IDP interactions, if it is possible to generalize at all. Finally, kinetic mechanisms that invoke conformational selection and/or induced fit are often used to characterize coupled IDP folding and binding, although application of these models is typically built upon thermodynamic observations. Recently, the reaction rates and kinetic mechanisms of more intrinsically disordered systems have been tested through rigorous kinetic experiments. Motivated by these exciting advances, here we provide a review and prospectus for the quantitative study of IDP structure, thermodynamics, and kinetics.

Original languageEnglish (US)
Pages (from-to)1314-1326
Number of pages13
JournalBiochemistry
Volume54
Issue number6
DOIs
StatePublished - Feb 17 2015

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Intrinsically Disordered Proteins
Thermodynamics
Kinetics
Biophysics
Cell signaling
Biological Phenomena
Protein folding
Protein Databases
Biochemistry
Electrostatic force
Protein Folding
Transcription
Static Electricity
Protein Binding
Reaction kinetics
Reaction rates
Proteins
Growth
Research

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

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Quantitative biophysical characterization of intrinsically disordered proteins. / Gibbs, Eric B.; Showalter, Scott A.

In: Biochemistry, Vol. 54, No. 6, 17.02.2015, p. 1314-1326.

Research output: Contribution to journalArticle

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