ArticleProceedings of the National Academy of Sciences of the United States of America2013
Misplaced helix slows down ultrafast pressure-jump protein folding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 53 citations in OpenAlex.
- Structure of a transient protein-folding intermediate by pressure-jump NMR spectroscopy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Advances in Mixer Design and Detection Methods for Kinetics Studies of Macromolecular Folding and Binding on the Microsecond Time Scale.Molecules (Basel, Switzerland) · 2022Article
- Fast pressure-jump all-atom simulations and experiments reveal site-specific protein dehydration-folding dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Practical aspects of high-pressure NMR spectroscopy and its applications in protein biophysics and structural biology.Methods (San Diego, Calif.) · 2018Article
- On the Origin of Microtubules' High-Pressure Sensitivity.Biophysical journal · 2018Article
- Simulated pressure denaturation thermodynamics of ubiquitin.Biophysical chemistry · 2017Article
- Pressure modulates the self-cleavage step of the hairpin ribozyme.Nature communications · 2017Article
- Protein unfolding mechanisms and their effects on folding experiments.F1000Research · 2017Review
- Water Determines the Structure and Dynamics of Proteins.Chemical reviews · 2016Review
- Cooperative folding near the downhill limit determined with amino acid resolution by hydrogen exchange.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Fast-folding proteins under stress.Cellular and molecular life sciences : CMLS · 2015Review
- Comparing Fast Pressure Jump and Temperature Jump Protein Folding Experiments and Simulations.Journal of the American Chemical Society · 2015Article
- Fast protein folding kinetics.Quarterly reviews of biophysics · 2014Review
- Observation of complete pressure-jump protein refolding in molecular dynamics simulation and experiment.Journal of the American Chemical Society · 2014Article
- Transient non-native helix formation during the folding of β-lactoglobulin.Biomolecules · 2014Review
- Transition state and ground state properties of the helix-coil transition in peptides deduced from high-pressure studies.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Advances in turbulent mixing techniques to study microsecond protein folding reactions.Biopolymers · 2013Article
- Engineering folding dynamics from two-state to downhill: application to λ-repressor.The journal of physical chemistry. B · 2013Article
- Native contacts determine protein folding mechanisms in atomistic simulations.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Dodine as a protein denaturant: the best of two worlds?The journal of physical chemistry. B · 2013Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Using a newly developed microsecond pressure-jump apparatus, we monitor the refolding kinetics of the helix-stabilized five-helix bundle protein λ*YA, the Y22W/Q33Y/G46,48A mutant of λ-repressor fragment 6-85, from 3 μs to 5 ms after a 1,200-bar P-drop. In addition to a microsecond phase, we observe a slower 1.4-ms phase during refolding to the native state. Unlike temperature denaturation, pressure denaturation produces a highly reversible helix-coil-rich state. This difference highlights the importance of the denatured initial condition in folding experiments and leads us to assign a compact nonnative helical trap as the reason for slower P-jump-induced refolding. To complement the experiments, we performed over 50 μs of all-atom molecular dynamics P-drop refolding simulations with four different force fields. Two of the force fields yield compact nonnative states with misplaced α-helix content within a few microseconds of the P-drop. Our overall conclusion from experiment and simulation is that the pressure-denatured state of λ*YA contains mainly residual helix and little β-sheet; following a fast P-drop, at least some λ*YA forms misplaced helical structure within microseconds. We hypothesize that nonnative helix at helix-turn interfaces traps the protein in compact nonnative conformations. These traps delay the folding of at least some of the population for 1.4 ms en route to the native state. Based on molecular dynamics, we predict specific mutations at the helix-turn interfaces that should speed up refolding from the pressure-denatured state, if this hypothesis is correct.
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