ArticleProceedings of the National Academy of Sciences of the United States of America2015
Random coil negative control reproduces the discrepancy between scattering and FRET measurements of denatured protein dimensions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Determinants of Protein Folding Pathways: Lessons from Metamorphic Proteins.International journal of molecular sciences · 2026Review
- Determination of absolute intramolecular distances in proteins using anomalous X-ray scattering interferometry.Nanoscale · 2025Article
- Sequence-dependent conformational preferences of disordered single-stranded RNA.Cell reports. Physical science · 2024Article
- The Action of Chemical Denaturants: From Globular to Intrinsically Disordered Proteins.Biology · 2023Review
- Effects of Sequence Composition, Patterning and Hydrodynamics on the Conformation and Dynamics of Intrinsically Disordered Proteins.International journal of molecular sciences · 2023Article
- Quantitative Description of Intrinsically Disordered Proteins Using Single-Molecule FRET, NMR, and SAXS.Journal of the American Chemical Society · 2021Article
- Where Biology and Traditional Polymers Meet: The Potential of Associating Sequence-Defined Polymers for Materials Science.JACS Au · 2021Review
- Integrating single-molecule spectroscopy and simulations for the study of intrinsically disordered proteins.Methods (San Diego, Calif.) · 2021Article
- Physics of the Nuclear Pore Complex: Theory, Modeling and Experiment.Physics reports · 2021Article
- Water as a Good Solvent for Unfolded Proteins: Folding and Collapse are Fundamentally Different.Journal of molecular biology · 2020Review
- Protein structural changes characterized by high-pressure, pulsed field gradient diffusion NMR spectroscopy.Journal of magnetic resonance (San Diego, Calif. : 1997) · 2020Article
- Emerging consensus on the collapse of unfolded and intrinsically disordered proteins in water.Current opinion in structural biology · 2020Review
- Commonly used FRET fluorophores promote collapse of an otherwise disordered protein.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Exploring the colloid-to-polymer transition for ultra-low crosslinked microgels from three to two dimensions.Nature communications · 2019Article
- Single Molecule FRET: A Powerful Tool to Study Intrinsically Disordered Proteins.Biomolecules · 2018Review
- Disordered linkers in multidomain allosteric proteins: Entropic effect to favor the open state or enhanced local concentration to favor the closed state?Protein science : a publication of the Protein Society · 2018Article
- Comment on "Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water".Science (New York, N.Y.) · 2018Article
- Comment on "Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water".Science (New York, N.Y.) · 2018Article
- Hypothesis: structural heterogeneity of the unfolded proteins originating from the coupling of the local clusters and the long-range distance distribution.Biophysical reviews · 2018Review
- Exploring the Denatured State Ensemble by Single-Molecule Chemo-Mechanical Unfolding: The Effect of Force, Temperature, and Urea.Journal of molecular biology · 2018Article
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6 authors.
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Abstract
Small-angle scattering studies generally indicate that the dimensions of unfolded single-domain proteins are independent (to within experimental uncertainty of a few percent) of denaturant concentration. In contrast, single-molecule FRET (smFRET) studies invariably suggest that protein unfolded states contract significantly as the denaturant concentration falls from high (∼6 M) to low (∼1 M). Here, we explore this discrepancy by using PEG to perform a hitherto absent negative control. This uncharged, highly hydrophilic polymer has been shown by multiple independent techniques to behave as a random coil in water, suggesting that it is unlikely to expand further on the addition of denaturant. Consistent with this observation, small-angle neutron scattering indicates that the dimensions of PEG are not significantly altered by the presence of either guanidine hydrochloride or urea. smFRET measurements on a PEG construct modified with the most commonly used FRET dye pair, however, produce denaturant-dependent changes in transfer efficiency similar to those seen for a number of unfolded proteins. Given the vastly different chemistries of PEG and unfolded proteins and the significant evidence that dye-free PEG is well-described as a denaturant-independent random coil, this similarity raises questions regarding the interpretation of smFRET data in terms of the hydrogen bond- or hydrophobically driven contraction of the unfolded state at low denaturant.
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