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

No organism can survive across the entire temperature range found in the bi osphere, and a given species can rarely support active metabolism across mo re than a few tens of degreesC. Nevertheless, life can be maintained at sur prisingly extreme temperatures, from below -50 to over 110 degreesC. That p roteins, which are assembled with the same 20 amino acids in all species, c an 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 mo difications or structural motifs that explain the ability of these molecule s 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 h ot 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. Stabili ty is needed to ensure the appropriate geometry for ligand binding, as well as to avoid denaturation, while flexibility is necessary to allow catalysi s at a metabolically appropriate rate. Comparisons of homologous proteins f rom 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 functio ns. (C) 2001 Elsevier Science Inc. All rights reserved.