ArticleNucleic acids research2018
Protein plasticity driven by disorder and collapse governs the heterogeneous binding of CytR to DNA.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Article
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- Functional regulation of an intrinsically disordered protein via a conformationally excited state.Science advances · 2023Article
- Flexible Target Recognition of the Intrinsically Disordered DNA-Binding Domain of CytR Monitored by Single-Molecule Fluorescence Spectroscopy.The journal of physical chemistry. B · 2022Article
- Quantification of Entropic Excluded Volume Effects Driving Crowding-Induced Collapse and Folding of a Disordered Protein.The journal of physical chemistry letters · 2022Article
- Slow Folding of a Helical Protein: Large Barriers, Strong Internal Friction, or a Shallow, Bumpy Landscape?The journal of physical chemistry. B · 2020Article
- Controlling Structure and Dimensions of a Disordered Protein via Mutations.Biochemistry · 2020Article
- Information theoretic measures for quantifying sequence-ensemble relationships of intrinsically disordered proteins.Protein engineering, design & selection : PEDS · 2019Article
- Thermally versus Chemically Denatured Protein States.Biochemistry · 2019Article
- Engineering Order and Cooperativity in a Disordered Protein.Biochemistry · 2019Article
- A binding cooperativity switch driven by synergistic structural swelling of an osmo-regulatory protein pair.Nature communications · 2019Article
- Intrinsically disordered proteins in crowded milieu: when chaos prevails within the cellular gumbo.Cellular and molecular life sciences : CMLS · 2018Review
- Tunable order-disorder continuum in protein-DNA interactions.Nucleic acids research · 2018Article
- Entropic Control of an Excited Folded-Like Conformation in a Disordered Protein Ensemble.Journal of molecular biology · 2018Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The amplitude of thermodynamic fluctuations in biological macromolecules determines their conformational behavior, dimensions, nature of phase transitions and effectively their specificity and affinity, thus contributing to fine-tuned molecular recognition. Unique among large-scale conformational changes in proteins are temperature-induced collapse transitions in intrinsically disordered proteins (IDPs). Here, we show that CytR DNA-binding domain, an IDP that folds on binding DNA, undergoes a coil-to-globule transition with temperature in the absence of DNA while exhibiting energetically decoupled local and global structural rearrangements, and maximal thermodynamic fluctuations at the optimal bacterial growth temperature. The collapse is shown to be a continuous transition through a combination of statistical-mechanical modeling and all-atom implicit solvent simulations. Surprisingly, CytR binds single-site cognate DNA with negative cooperativity, described by Hill coefficients less than one, resulting in a graded binding response. We show that heterogeneity arising from varying binding-competent CytR conformations or orientations at the single-molecular level contributes to negative binding cooperativity at the level of bulk measurements due to the conflicting requirements of collapse transition, large fluctuations and folding-upon-binding. Our work reports strong evidence for functionally driven thermodynamic fluctuations in determining the extent of collapse and disorder with implications in protein search efficiency of target DNA sites and regulation.
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