ArticleProceedings of the National Academy of Sciences of the United States of America2014
Role of cavities and hydration in the pressure unfolding of T4 lysozyme.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed.
- Hydraulic Activation of the AsLOV2 Photoreceptor.bioRxiv : the preprint server for biology · 2025Article
- Advances in utilizing reverse micelles to investigate membrane proteins.Biochemical Society transactions · 2024Review
- A pressure-jump EPR system to monitor millisecond conformational exchange rates of spin-labeled proteins.Protein science : a publication of the Protein Society · 2024Article
- Solution NMR investigations of integral membrane proteins: Challenges and innovations.Current opinion in structural biology · 2023Review
- High-Pressure Processing of Human Milk: A Balance between Microbial Inactivation and Bioactive Protein Preservation.The Journal of nutrition · 2023Article
- Inside Out Computational Redesign of Cavities for Improving Thermostability and Catalytic Activity ofApplied and environmental microbiology · 2023Article
- Pressure, motion, and conformational entropy in molecular recognition by proteins.Biophysical reports · 2023Article
- Familial Alzheimer's Disease-Related Mutations Differentially Alter Stability of Amyloid-Beta Aggregates.The journal of physical chemistry letters · 2023Article
- High Pressure CPMG and CEST Reveal That Cavity Position Dictates Distinct Dynamic Disorder in the PP32 Repeat Protein.The journal of physical chemistry. B · 2022Article
- Automated Path Searching Reveals the Mechanism of Hydrolysis Enhancement by T4 Lysozyme Mutants.International journal of molecular sciences · 2022Article
- Pressure Adaptations in Deep-SeaBiology · 2021Article
- Thermodynamic stability of hnRNP A1 low complexity domain revealed by high-pressure NMR.Proteins · 2021Article
- Protein structural changes characterized by high-pressure, pulsed field gradient diffusion NMR spectroscopy.Journal of magnetic resonance (San Diego, Calif. : 1997) · 2020Article
- How internal cavities destabilize a protein.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Site-Resolved and Quantitative Characterization of Very Weak Protein-Ligand Interactions.ACS chemical biology · 2019Article
- Water loading driven size, shape, and composition of cetyltrimethylammonium/hexanol/pentane reverse micelles.Journal of colloid and interface science · 2019Article
- Void distributions reveal structural link between jammed packings and protein cores.Physical review. E · 2019Article
- Reverse Micelle Encapsulation of Proteins for NMR Spectroscopy.Methods in enzymology · 2019Article
- Enzymes from piezophiles.Seminars in cell & developmental biology · 2018Review
- Inhibitor potency varies widely among tumor-relevant human isocitrate dehydrogenase 1 mutants.The Biochemical journal · 2018Article
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Abstract
It is well known that high hydrostatic pressures can induce the unfolding of proteins. The physical underpinnings of this phenomenon have been investigated extensively but remain controversial. Changes in solvation energetics have been commonly proposed as a driving force for pressure-induced unfolding. Recently, the elimination of void volumes in the native folded state has been argued to be the principal determinant. Here we use the cavity-containing L99A mutant of T4 lysozyme to examine the pressure-induced destabilization of this multidomain protein by using solution NMR spectroscopy. The cavity-containing C-terminal domain completely unfolds at moderate pressures, whereas the N-terminal domain remains largely structured to pressures as high as 2.5 kbar. The sensitivity to pressure is suppressed by the binding of benzene to the hydrophobic cavity. These results contrast to the pseudo-WT protein, which has a residual cavity volume very similar to that of the L99A-benzene complex but shows extensive subglobal reorganizations with pressure. Encapsulation of the L99A mutant in the aqueous nanoscale core of a reverse micelle is used to examine the hydration of the hydrophobic cavity. The confined space effect of encapsulation suppresses the pressure-induced unfolding transition and allows observation of the filling of the cavity with water at elevated pressures. This indicates that hydration of the hydrophobic cavity is more energetically unfavorable than global unfolding. Overall, these observations point to a range of cooperativity and energetics within the T4 lysozyme molecule and illuminate the fact that small changes in physical parameters can significantly alter the pressure sensitivity of proteins.
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