Review: Protein function at thermal extremes: balancing stability and flexibility

Comp Biochem Physiol A Mol Integr Physiol. 2001 Jun;129(2-3):417-31. doi: 10.1016/s1095-6433(00)00359-7.


No organism can survive across the entire temperature range found in the biosphere, and a given species can rarely support active metabolism across more than a few tens of degrees C. Nevertheless, life can be maintained at surprisingly extreme temperatures, from below -50 to over 110 degrees C. That proteins, which are assembled with the same 20 amino acids in all species, can function well at both extremes of this range illustrates the plasticity available in the construction of these macromolecules. In studying proteins from extremophiles, researchers have found no new amino acids, covalent modifications or structural motifs that explain the ability of these molecules to function in such harsh environments. Rather, subtle redistributions of the same intramolecular interactions required for protein stabilization at moderate temperatures are sufficient to maintain structural integrity at hot or cold extremes. The key to protein function, whether in polar seas or hot springs, is the maintenance of an appropriate balance between molecular stability on the one hand and structural flexibility on the other. Stability is needed to ensure the appropriate geometry for ligand binding, as well as to avoid denaturation, while flexibility is necessary to allow catalysis at a metabolically appropriate rate. Comparisons of homologous proteins from organisms spanning a wide range of thermal habitats show that adaptive mutations, as well as stabilizing solutes, maintain a balance between these two attributes, regardless of the temperature at which the protein functions.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Amino Acids / chemistry
  • Animals
  • Enzyme Stability*
  • Enzymes / chemistry
  • Enzymes / physiology
  • Molecular Sequence Data
  • Proteins / chemistry*
  • Proteins / physiology*
  • Temperature*


  • Amino Acids
  • Enzymes
  • Proteins