Cited by 135Protein Structure and DynamicsRNA and protein synthesis mechanismsAdvanced Physical and Chemical Molecular Interactions

Describing sequence–ensemble relationships for intrinsically disordered proteins

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Mao, Albert H., Lyle, Nicholas, Pappu, Rohit V.·2013·Biochemical Journal

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.

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  • In addition to being sequence-specific, the features of conformational ensembles can only be described in terms of single- or multi-parameter distribution functions and/or moments of these distributions.

    “in addition to being sequence-specific, the features of conformational ensembles can only be described in terms of single-or multi-parameter distribution functions and/or moments of these distributions.79”

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Authors
Mao, A. H., Lyle, N., & Pappu, R. V.
Affiliations
Washington University in St. Louis (US)
Corresponding author
Pappu, Rohit V.
Venue
Biochemical Journal
Published
2012-12-14
Volume
449
Issue
2
Pages
307-318
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
OpenAlex
W2079994402
Cited by
135
References
191
Citations by year
2026: 4 · 2025: 7 · 2024: 13 · 2023: 12 · 2022: 9 · 2021: 10 · 2020: 11 · 2019: 10 · 2018: 12 · 2017: 9 · 2016: 5 · 2015: 8 · 2014: 13 · 2013: 12
FWCI
0.96
Type
journal article
Language
en
Open access
Locations
  • Biochemical Journal (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation
  • Foundation for the National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS056114)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Advanced Physical and Chemical Molecular Interactions
Keywords
intrinsically disordered proteins, conformational ensembles, protein conformational dynamics, structure-function relationship, protein-protein interaction, protein-nucleic acid interactions, polymer physics, quantitative framework
MeSH terms
Binding Sites, Models, Molecular, Peptides, Protein Binding, Protein Conformation, Proteins, Solvents, Thermodynamics, Protein Structure, Tertiary, Protein Folding

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