Structural differences between mesophilic, moderately thermophilic and extremely thermophilic protein subunits: results of a comprehensive survey

Background: Proteins from thermophilic organisms usually show high intrinsi c thermal stability but have structures that are very similar to their meso philic homologues. From prevous studies it is difficult to draw general con clusions about the structural features underlying the increased thermal sta bility of thermophilic proteins. Results: In order to reveal the general evolutionary strategy for changing the heat stability of proteins, a non-redundant data set was compiled compr ising all high-quality structures of thermophilic proteins and their mesoph ilic homologues from the Protein Data Bank. The selection (quality) criteri a were met by 64 mesophilic and 29 thermophilic protein subunits, represent ing 25 protein families. From the atomic coordinates, 13 structural paramet ers were calculated, compared and evaluated using statistical methods. This study is distinguished from earlier ones by the strict quality control of the structures used and the size of the data set. Conclusions: Different protein families adapt to higher temperatures by dif ferent sets of structural devices. Regarding the structural parameters, the only generally observed rule is an increase in the number of ion pairs wit h increasing growth temperature. Other parameters show just a trend, wherea s the number of hydrogen bonds and the polarity of buried surfaces exhibit no clear-cut tendency to change with growth temperature. Proteins from extr eme thermophiles are stabilized in different ways to moderately thermophili c ones. The preferences of these two groups are different with regards to t he number of ion pairs, the number of cavities, the polarity of exposed sur face and the secondary structural composition.