ArticleProceedings of the National Academy of Sciences of the United States of America2012
Exploring one-state downhill protein folding in single molecules.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 55 citations in OpenAlex.
- Model-free photon analysis of diffusion-based single-molecule FRET experiments.Nature communications · 2025Article
- Molten globule-like transition state of protein barnase measured with calorimetric force spectroscopy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Diverse Folding Pathways of HIV-1 Protease Monomer on a Rugged Energy Landscape.Biophysical journal · 2019Article
- Ultrafast folding kinetics of WW domains reveal how the amino acid sequence determines the speed limit to protein folding.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Diffusion-limited association of disordered protein by non-native electrostatic interactions.Nature communications · 2018Article
- Protein folding transition path times from single molecule FRET.Current opinion in structural biology · 2018Review
- pH-Dependent cooperativity and existence of a dry molten globule in the folding of a miniprotein BBL.Physical chemistry chemical physics : PCCP · 2018Article
- Conformational Heterogeneity and FRET Data Interpretation for Dimensions of Unfolded Proteins.Biophysical journal · 2017Article
- How cooperative are protein folding and unfolding transitions?Protein science : a publication of the Protein Society · 2016Review
- When fast is better: protein folding fundamentals and mechanisms from ultrafast approaches.The Biochemical journal · 2016Review
- Meandering Down the Energy Landscape of Protein Folding: Are We There Yet?Biophysical journal · 2016Review
- Monitoring the heat-induced structural changes of alkaline phosphatase by molecular modeling, fluorescence spectroscopy and inactivation kinetics investigations.Journal of food science and technology · 2015Article
- A Method for Extracting the Free Energy Surface and Conformational Dynamics of Fast-Folding Proteins from Single Molecule Photon Trajectories.The journal of physical chemistry. B · 2015Article
- Shedding light on protein folding landscapes by single-molecule fluorescence.Chemical Society reviews · 2014Review
- Kinetics of fast changing intramolecular distance distributions obtained by combined analysis of FRET efficiency kinetics and time-resolved FRET equilibrium measurements.Biophysical journal · 2014Article
- Reply to Campos and Muñoz: Why phosphate is a bad buffer for guanidinium chloride titrations.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Reply to Huang et al.: Slow proton exchange can duplicate the number of species observed in single-molecule experiments of protein folding.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Don't waste good methods on bad buffers and ambiguous data.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Article
- Equilibrium unfolding of the PDZ domain of β2-syntrophin.Biophysical journal · 2012Article
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7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A one-state downhill protein folding process is barrierless at all conditions, resulting in gradual melting of native structure that permits resolving folding mechanisms step-by-step at atomic resolution. Experimental studies of one-state downhill folding have typically focused on the thermal denaturation of proteins that fold near the speed limit (ca. 10(6) s(-1)) at their unfolding temperature, thus being several orders of magnitude too fast for current single-molecule methods, such as single-molecule FRET. An important open question is whether one-state downhill folding kinetics can be slowed down to make them accessible to single-molecule approaches without turning the protein into a conventional activated folder. Here we address this question on the small helical protein BBL, a paradigm of one-state downhill thermal (un)folding. We decreased 200-fold the BBL folding-unfolding rate by combining chemical denaturation and low temperature, and carried out free-diffusion single-molecule FRET experiments with 50-μs resolution and maximal photoprotection using a recently developed Trolox-cysteamine cocktail. These experiments revealed a single conformational ensemble at all denaturing conditions. The chemical unfolding of BBL was then manifested by the gradual change of this unique ensemble, which shifts from high to low FRET efficiency and becomes broader at increasing denaturant. Furthermore, using detailed quantitative analysis, we could rule out the possibility that the BBL single-molecule data are produced by partly overlapping folded and unfolded peaks. Thus, our results demonstrate the one-state downhill folding regime at the single-molecule level and highlight that this folding scenario is not necessarily associated with ultrafast kinetics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.