ArticleProceedings of the National Academy of Sciences of the United States of America2012
Cavities determine the pressure unfolding of proteins.
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 149 papers.
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149 citing papers in PubMed.
- Functionally related internal fluctuations in human ileal bile acid-binding protein by high pressure nuclear magnetic resonance.Protein science : a publication of the Protein Society · 2026Article
- Small Molecule Regulation of CLOCK:BMAL1 DNA Binding Activity.bioRxiv : the preprint server for biology · 2026Article
- Adaptation of Folding and Function of a Nuclease from the Cold Deep Sea.Journal of molecular biology · 2026Article
- Effect of high hydrostatic pressure on D-amino acid oxidase activity and stability.Journal of biological engineering · 2026Article
- Acidification and Calcium Addition Effects on High-Pressure and Thermally Induced Pulse Protein Gels.Gels (Basel, Switzerland) · 2025Article
- Hydraulic Activation of the AsLOV2 Photoreceptor.bioRxiv : the preprint server for biology · 2025Article
- 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
- Sequence Determinants of Allosteric Back-to-front Control of the Arf Nucleotide Switch.Journal of molecular biology · 2025Article
- Function and Engineering of a Food Enzyme Under Coupled High-Temperature-Pressure Conditions: Insights from Molecular Dynamics Simulation and Experimental Validation.Foods (Basel, Switzerland) · 2025Article
- Broken but not beaten: Challenge of reducing the amyloids pathogenicity by degradation.Journal of advanced research · 2025Review
- Extremophilic hemoglobins: The structure of Shewanella benthica truncated hemoglobin N.The Journal of biological chemistry · 2025Article
- High hydrostatic pressure promotes gene transcription via a cystathionine-β-synthase domain-containing protein in the hyperthermophilic archaeon Pyrococcus yayanosii.Nucleic acids research · 2025Article
- In Silico Strategies for Characterizing Inner Cavities of Lipid-Binding Proteins.Methods in molecular biology (Clifton, N.J.) · 2025Article
- A pressure-jump EPR system to monitor millisecond conformational exchange rates of spin-labeled proteins.Protein science : a publication of the Protein Society · 2024Article
- Differential Responses in the Core, Active Site and Peripheral Regions of Cytochrome c Peroxidase to Extreme Pressure and Temperature.Journal of molecular biology · 2024Article
- Extremophiles and Extremophilic Behaviour-New Insights and Perspectives.Life (Basel, Switzerland) · 2024Review
- A molten globule ensemble primes Arf1-GDP for the nucleotide switch.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Probing the structural stability of R-phycocyanin under pressure.Protein science : a publication of the Protein Society · 2024Article
- NMR Dynamic View of the Stabilization of the WW4 Domain by Neutral NaCl and Kosmotropic NaInternational journal of molecular sciences · 2024Article
- Fundamental Aspects of Phase-Separated Biomolecular Condensates.Chemical reviews · 2024Review
89 more citing papers are in PubMed but not listed here.
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9 authors.
Funding
Abstract
It has been known for nearly 100 years that pressure unfolds proteins, yet the physical basis of this effect is not understood. Unfolding by pressure implies that the molar volume of the unfolded state of a protein is smaller than that of the folded state. This decrease in volume has been proposed to arise from differences between the density of bulk water and water associated with the protein, from pressure-dependent changes in the structure of bulk water, from the loss of internal cavities in the folded states of proteins, or from some combination of these three factors. Here, using 10 cavity-containing variants of staphylococcal nuclease, we demonstrate that pressure unfolds proteins primarily as a result of cavities that are present in the folded state and absent in the unfolded one. High-pressure NMR spectroscopy and simulations constrained by the NMR data were used to describe structural and energetic details of the folding landscape of staphylococcal nuclease that are usually inaccessible with existing experimental approaches using harsher denaturants. Besides solving a 100-year-old conundrum concerning the detailed structural origins of pressure unfolding of proteins, these studies illustrate the promise of pressure perturbation as a unique tool for examining the roles of packing, conformational fluctuations, and water penetration as determinants of solution properties of proteins, and for detecting folding intermediates and other structural details of protein-folding landscapes that are invisible to standard experimental approaches.
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