Thermal Adaptations of DNA-Binding Proteins

Adaptations of thermophilic microorganisms to high environmental temperatures have been under extensive study for years [1]. These efforts have provided valuable insight into the biology of thermophiles and clarified how various components of the cell have adapted to their extreme living conditions. However, the cell is a complicated system; not only do individual components but also the complexes of them need to have enhanced stability amidst high temperatures. Protein-DNA interactions play crucial roles in the living cell. A number of vital processes such as chromosomal replication, transcriptional regulation and mismatch repair require proper protein-DNA interactions. Although thermodynamic characterization of several thermophilic DNA-binding proteins has revealed that the temperature of maximal binding affinity of these proteins are significantly higher than that of mesophilic proteins [3], little is known about molecular mechanisms of the thermal adaptations of protein-DNA interactions. Here we collected DNA-binding proteins from several thermophilic bacteria and compared their DNA-binding interfaces with mesophilic orthologs. Analyses of amino acid substitutions at DNAbinding interfaces revealed thermophilic proteins have enhanced electrostatic complementarity at their DNA-binding sites.