Is the hydrophobic effect stabilizing or destabilizing in proteins? The contribution of disulphide bonds to protein stability

J Mol Biol. 1991 Jan 20;217(2):389-98. doi: 10.1016/0022-2836(91)90551-g.

Abstract

It has been recently concluded that the hydrophobic effect, hitherto regarded as a major driving force in the folding of proteins, destabilizes the folded state relative to the unfolded state. We summarize the properties of the hydrophobic effect obtained from solvent transfer experiments and show that the recent conclusion is an artifact of crosslinking in the unfolded state, caused by disulphide bonds, metals or cofactors. We show that, for the proteins in the data set, crosslinks surprisingly destabilize folded structures entropically, but stabilize them enthalpically to a greater extent. We also calculate non-polar surface areas of these unfolded proteins. These surface areas are decreased by crosslinks. The unfolded state of proteins lacking constraints, such as myoglobin, is well approximated by a mixture of residues containing alpha-helical and beta-sheet dihedral angles. Surface areas of unfolded proteins cannot be obtained by summing the surface areas of individual residues, since this ignores any unavoidable side-chain-side-chain interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Disulfides / chemistry*
  • Heme / chemistry
  • Hydrocarbons / chemistry
  • Metalloproteins / chemistry
  • Muramidase / chemistry
  • Myoglobin / chemistry
  • Protein Conformation*
  • Proteins / chemistry*
  • Solvents
  • Surface Properties
  • Thermodynamics
  • Water

Substances

  • Disulfides
  • Hydrocarbons
  • Metalloproteins
  • Myoglobin
  • Proteins
  • Solvents
  • Water
  • Heme
  • Muramidase