How do thermophilic proteins deal with heat?

Cell Mol Life Sci. 2001 Aug;58(9):1216-33. doi: 10.1007/PL00000935.


Recent years have witnessed an explosion of sequence and structural information for proteins from hyperthermophilic and thermophilic organisms. Complete genome sequences are available for many hyperthermophilic archaeons. Here, we review some recent studies on protein thermostability along with work from our laboratory. A large number of sequence and structural factors are thought to contribute toward higher intrinsic thermal stability of proteins from these organisms. The most consistent are surface loop deletion, increased occurrence of hydrophobic residues with branched side chains and an increased proportion of charged residues at the expense of uncharged polar residues. The energetic contribution of electrostatic interactions such as salt bridges and their networks toward protein stability can be stabilizing or destabilizing. For hyperthermophilic proteins, the contribution is mostly stabilizing. Macroscopically, improvement in electrostatic interactions and strengthening of hydrophobic cores by branched apolar residues increase the enthalpy change between the folded and unfolded states of a thermophilic protein. At the same time, surface loop deletion contributes to decreased conformational entropy and decreased heat capacity change between the folded and unfolded states of the protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Archaea / genetics
  • Archaea / physiology*
  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / genetics
  • Archaeal Proteins / physiology*
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / physiology*
  • Enzymes / chemistry
  • Gram-Negative Bacteria / genetics
  • Gram-Negative Bacteria / physiology*
  • Models, Molecular
  • Protein Conformation
  • Thermococcales / genetics
  • Thermococcales / physiology*
  • Thermodynamics


  • Archaeal Proteins
  • Bacterial Proteins
  • Enzymes