Cavities determine the pressure unfolding of proteins
Julien Roche,Jose A. Caro,Douglas R. Norberto,Philippe Barthe,Christian Roumestand,Jamie L. Schlessman,Angel E. Garcia,E Bertrand García-Moreno,Catherine A. Royer +8 more
TLDR
The promise of pressure perturbation is illustrated 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.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 approachesread more
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Water Determines the Structure and Dynamics of Proteins
Marie-Claire Bellissent-Funel,Ali Hassanali,Martina Havenith,Richard H. Henchman,Peter Pohl,Fabio Sterpone,David van der Spoel,Yao Xu,Angel E. Garcia +8 more
TL;DR: A review of the experimental and computational advances over the past decade in understanding the role of water in the dynamics, structure, and function of proteins focuses on the combination of X-ray and neutron crystallography, NMR, terahertz spectroscopy, mass spectroscopic, thermodynamics, and computer simulations to reveal how water assist proteins in their function.
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Experimental Binding Energies in Supramolecular Complexes
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Protein aggregation and its impact on product quality.
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References
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Denaturant m values and heat capacity changes: relation to changes in accessible surface areas of protein unfolding.
TL;DR: Denaturant m values, the dependence of the free energy of unfolding on denaturant concentration, have been collected for a large set of proteins and correlate very strongly with the amount of protein surface exposed to solvent upon unfolding.
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Stability of protein structure and hydrophobic interaction.
TL;DR: This chapter focuses on the stability of protein structure and hydrophobic interaction, and examines the main achievements of microcalorimetric studies of protein denaturation and of the dissolution of nonpolar substances in water.
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Temperature dependence of the hydrophobic interaction in protein folding
TL;DR: The hydrocarbon model predicts that plots of the specific entropy change on unfolding versus temperature should nearly intersect close to 113 degrees C, as observed by Privalov.
Journal ArticleDOI
The pressure dependence of hydrophobic interactions is consistent with the observed pressure denaturation of proteins.
Gerhard Hummer,Shekhar Garde,Shekhar Garde,Angel E. Garcia,Michael E. Paulaitis,Lawrence R. Pratt +5 more
TL;DR: The pressure denaturation puzzle is resolved by focusing on the pressure-dependent transfer of water into the protein interior, in contrast to the transfer of nonpolar residues into water, the approach commonly taken in models of protein unfolding.
The pressure dependence of hydrophobic interactions is consistent with the observed pressure denaturation of proteins (protein foldingyprotein folding kineticsyhydrophobic effectyactivation volumesyprotein unfolding)
TL;DR: In this paper, the authors focus on the pressure-dependent transfer of water into the protein interior, in contrast to the transfer of nonpolar residues into water, theapproach commonly taken in models of protein unfolding.