Pressure—A Gateway to Fundamental Insights into Protein Solvation, Dynamics, and Function

Luong, Trung Quan; Kapoor, Shobhna; Winter, Roland

doi:10.1002/cphc.201500669

Cited by 89 publications

(94 citation statements)

References 131 publications

(173 reference statements)

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“…Since τ bulk most probably reflects the interaction between bulk water and hydration layer, it indicates that even the characteristics of water can slightly change under high pressure application on a living cell due to an increased crowding. These properties are quite peculiar, as experiments on water in presence or absence of proteins4951 show that there should be no difference in the diffusion coefficients D of water in the temperature/pressure range explored in the present study. Our results clearly suggest that the specific adaptation to high pressure in T. barophilus is done via the modification of the hydration layer properties combined with an increased protein flexibility.…”

Section: Discussionmentioning

confidence: 60%

“…Our results suggest that T. barophilus could produce these osmolytes to slow down hydration water and to reduce the hydration layer in order to maintain the biomolecules functional. It is known that organic osmolytes, by modifying the properties of the hydration water can stabilize proteins under different types of stress, including high pressure51. Indeed, MG has been shown to increase the rigidity of proteins under thermal stress59.…”

Section: Discussionmentioning

confidence: 99%

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High protein flexibility and reduced hydration water dynamics are key pressure adaptive strategies in prokaryotes

Martínez

Michoud

Cario

et al. 2016

Sci Rep

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Water and protein dynamics on a nanometer scale were measured by quasi-elastic neutron scattering in the piezophile archaeon Thermococcus barophilus and the closely related pressure-sensitive Thermococcus kodakarensis, at 0.1 and 40 MPa. We show that cells of the pressure sensitive organism exhibit higher intrinsic stability. Both the hydration water dynamics and the fast protein and lipid dynamics are reduced under pressure. In contrast, the proteome of T. barophilus is more pressure sensitive than that of T. kodakarensis. The diffusion coefficient of hydration water is reduced, while the fast protein and lipid dynamics are slightly enhanced with increasing pressure. These findings show that the coupling between hydration water and cellular constituents might not be simply a master-slave relationship. We propose that the high flexibility of the T. barophilus proteome associated with reduced hydration water may be the keys to the molecular adaptation of the cells to high hydrostatic pressure.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

High protein flexibility and reduced hydration water dynamics are key pressure adaptive strategies in prokaryotes

Martínez

Michoud

Cario

et al. 2016

Sci Rep

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“…On the other hand, pressure is an important physical control parameter in addition to temperature that can be used to determine thermodynamic and kinetic parameters, which are otherwise inaccessible89101112. Furthermore, a particularly promising field is the use of high hydrostatic pressure (HHP) to modulate enzymatic conversions131415. Given that the rate of an enzymatic reaction is often limited by the thermostability of the enzyme, superimposing pressure-induced thermostabilization of the enzyme with an accelerated substrate conversion at increased temperatures can lead to an improved overall reaction rate.…”

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confidence: 99%

Pressure modulates the self-cleavage step of the hairpin ribozyme

et al. 2017

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The ability of certain RNAs, denoted as ribozymes, to not only store genetic information but also catalyse chemical reactions gave support to the RNA world hypothesis as a putative step in the development of early life on Earth. This, however, might have evolved under extreme environmental conditions, including the deep sea with pressures in the kbar regime. Here we study pressure-induced effects on the self-cleavage of hairpin ribozyme by following structural changes in real-time. Our results suggest that compression of the ribozyme leads to an accelerated transesterification reaction, being the self-cleavage step, although the overall process is retarded in the high-pressure regime. The results reveal that favourable interactions between the reaction site and neighbouring nucleobases are strengthened under pressure, resulting therefore in an accelerated self-cleavage step upon compression. These results suggest that properly engineered ribozymes may also act as piezophilic biocatalysts in addition to their hitherto known properties.

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“…As high-pressure is well known to induce the dissociation of oligomeric proteins 37 , we also examined the effect of pressure on dimer dissociation ( K dimer ). We used the folding conditions optimized for the study of the monomeric protease 38 to prepare inhibitor-free PR D25N and recorded 2D 1 H- 15 N NMR spectra at a final dimer concentration of 14 and 75 μM.…”

Section: Resultsmentioning

confidence: 99%

Evolution under Drug Pressure Remodels the Folding Free-Energy Landscape of Mature HIV-1 Protease

Louis

Roche

2016

Journal of Molecular Biology

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Using high-pressure NMR spectroscopy and differential scanning calorimetry, we investigate the folding landscape of the mature HIV-1 protease homodimer. The cooperativity of unfolding was measured in the absence or presence of an active site inhibitor DMP323, for the active protease (PR), its inactive variant PRD25N and an extremely multi-drug resistant mutant, PR20. The individual fit of the pressure denaturation profiles gives rise to first order, ΔGNMR, and second order, ΔVNMR (the derivative of ΔGNMR with pressure) apparent thermodynamic parameters for each amide proton considered. Heterogeneity in the apparent ΔVNMR values reflects departure from an ideal cooperative unfolding transition. The narrow to broad distribution of ΔVNMR spanning the extremes from inhibitor-free PR20D25N to PR-DMP323 complex, and distinctively for PRD25N-DMP323 complex, indicated large variations in folding cooperativity. Consistent with this data, the shape of thermal unfolding transitions varies from asymmetric for PR to nearly symmetric for PR20, as dimer-inhibitor ternary complexes. Lack of structural cooperativity was observed between regions located close to the active site, including the hinge and tip of the glycine-rich flaps, and the rest of the protein. These results strongly suggest that inhibitor binding drastically decreases the cooperativity of unfolding by trapping the closed flap conformation in a deep energy minimum. To evade this conformational trap, PR20 evolves exhibiting a smoother folding landscape with nearly an ideal two-state (cooperative) unfolding transition. This study highlights the malleability of retroviral protease folding pathways by illustrating how the selection of mutations under drug pressure remodels the free-energy landscape as a primary mechanism.

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Pressure—A Gateway to Fundamental Insights into Protein Solvation, Dynamics, and Function

Cited by 89 publications

References 131 publications

High protein flexibility and reduced hydration water dynamics are key pressure adaptive strategies in prokaryotes

High protein flexibility and reduced hydration water dynamics are key pressure adaptive strategies in prokaryotes

Pressure modulates the self-cleavage step of the hairpin ribozyme

Evolution under Drug Pressure Remodels the Folding Free-Energy Landscape of Mature HIV-1 Protease

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