ArticleProceedings of the National Academy of Sciences of the United States of America2015
A hypothesis to reconcile the physical and chemical unfolding of proteins.
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 22 papers.
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Who cites it
22 citing papers in PubMed.
- Cancer-linked aggregation of p53 is driven by sequence-encoded frustration, solvation, and hydrophobic gating absent in its paralogs.Communications chemistry · 2026Article
- Article
- Review
- Thermodynamic stability of hnRNP A1 low complexity domain revealed by high-pressure NMR.Proteins · 2021Article
- Protein unfolded states populated at high and ambient pressure are similarly compact.Biophysical journal · 2021Article
- Combining High-Pressure Perturbation with NMR Spectroscopy for a Structural and Dynamical Characterization of Protein Folding Pathways.Molecules (Basel, Switzerland) · 2020Review
- Oncogenic Gain of Function in Glioblastoma Is Linked to Mutant p53 Amyloid Oligomers.iScience · 2020Article
- Sedimentation Yields Long-Term Stable Protein Samples as Shown by Solid-State NMR.Frontiers in molecular biosciences · 2020Article
- Single-molecule nanopore sensing of actin dynamics and drug binding.Chemical science · 2019Article
- Evolving SAXS versatility: solution X-ray scattering for macromolecular architecture, functional landscapes, and integrative structural biology.Current opinion in structural biology · 2019Review
- Practical aspects of high-pressure NMR spectroscopy and its applications in protein biophysics and structural biology.Methods (San Diego, Calif.) · 2018Article
- Aggregation-primed molten globule conformers of the p53 core domain provide potential tools for studying p53C aggregation in cancer.The Journal of biological chemistry · 2018Article
- Solution NMR investigation of the response of the lactose repressor core domain dimer to hydrostatic pressure.Biophysical chemistry · 2017Article
- The Role of Controlled Surface Topography and Chemistry on Mouse Embryonic Stem Cell Attachment, Growth and Self-Renewal.Materials (Basel, Switzerland) · 2017Article
- Modulation of polypeptide conformation through donor-acceptor transformation of side-chain hydrogen bonding ligands.Nature communications · 2017Article
- Structural basis for the dissociation of α-synuclein fibrils triggered by pressure perturbation of the hydrophobic core.Scientific reports · 2016Article
- Aggregation tendencies in the p53 family are modulated by backbone hydrogen bonds.Scientific reports · 2016Article
- The fluorescent monomeric protein Kusabira Orange. Pressure effect on its structure and stability.Biochemistry and biophysics reports · 2016Article
- Evolution under Drug Pressure Remodels the Folding Free-Energy Landscape of Mature HIV-1 Protease.Journal of molecular biology · 2016Article
- Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell.Chemical reviews · 2016Review
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2 authors.
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Abstract
High pressure (HP) or urea is commonly used to disturb folding species. Pressure favors the reversible unfolding of proteins by causing changes in the volumetric properties of the protein-solvent system. However, no mechanistic model has fully elucidated the effects of urea on structure unfolding, even though protein-urea interactions are considered to be crucial. Here, we provide NMR spectroscopy and 3D reconstructions from X-ray scattering to develop the "push-and-pull" hypothesis, which helps to explain the initial mechanism of chemical unfolding in light of the physical events triggered by HP. In studying MpNep2 from Moniliophthora perniciosa, we tracked two cooperative units using HP-NMR as MpNep2 moved uphill in the energy landscape; this process contrasts with the overall structural unfolding that occurs upon reaching a threshold concentration of urea. At subdenaturing concentrations of urea, we were able to trap a state in which urea is preferentially bound to the protein (as determined by NMR intensities and chemical shifts); this state is still folded and not additionally exposed to solvent [fluorescence and small-angle X-ray scattering (SAXS)]. This state has a higher susceptibility to pressure denaturation (lower p1/2 and larger ΔVu); thus, urea and HP share concomitant effects of urea binding and pulling and water-inducing pushing, respectively. These observations explain the differences between the molecular mechanisms that control the physical and chemical unfolding of proteins, thus opening up new possibilities for the study of protein folding and providing an interpretation of the nature of cooperativity in the folding and unfolding processes.
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