The Pressure Dependence of Hydrophobic Interactions is Consistent with the Observed Pressure Denaturation of Proteins

Proteins can be denatured by pressures of a few hundred MPa. This finding apparently contradicts the most widely used model of protein stability, where the formation of a hydrophobic core drives protein folding. The pressure denaturation puzzle is resolved by focusing on the pressure-dependent trans...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1998-02, Vol.95 (4), p.1552-1555
Main Authors: Hummer, Gerhard, Garde, Shekhar, Garcia, Angel E., Paulaitis, Michael E., Pratt, Lawrence R.
Format: Article
Language:English
Subjects:
Biochemistry
Biological Sciences
Free energy
Hydrostatic Pressure
Information theory
Kinetics
Mathematical minima
Methane
Methane - chemistry
Minimum contacts
Models, Chemical
Molecules
Physics
Protein Denaturation
Protein Folding
Proteins
Proteins - chemistry
Solubility
Solutes
Solvents
Thermodynamics
Water
Water pressure
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Summary:Proteins can be denatured by pressures of a few hundred MPa. This finding apparently contradicts the most widely used model of protein stability, where the formation of a hydrophobic core drives protein folding. 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. Pressure denaturation of proteins can then be explained by the pressure destabilization of hydrophobic aggregates by using an information theory model of hydrophobic interactions. Pressure-denatured proteins, unlike heat-denatured proteins, retain a compact structure with water molecules penetrating their core. Activation volumes for hydrophobic contributions to protein folding and unfolding kinetics are positive. Clathrate hydrates are predicted to form by virtually the same mechanism that drives pressure denaturation of proteins.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.95.4.1552