The pressure dependence of hydrophobic interactions is consistent with the observed pressure denaturation of proteins

Gerhard Hummer, Shekhar Garde, Angel E. García, Michael E. Paulaitis, Lawrence R. Pratt

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1552-1555
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number4
DOIs
StatePublished - Feb 17 1998

Keywords

  • Activation volumes
  • Hydrophobic effect
  • Protein folding
  • Protein folding kinetics
  • Protein unfolding

ASJC Scopus subject areas

  • General

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