Differences in Structural Rigidity between Thermophilic Proteins and their Mesophilic Homologues

Abstract

The source of increased stability in proteins from organisms that thrive in extreme thermal environments is not well understood. These proteins from thermophilic organisms can maintain biological functions at elevated temperatures which would render ordinary (mesophilic) proteins denatured and dysfunctional. Understanding the mechanisms responsible for thermostability has the potential to impact how effectively we can engineer thermostable analogues of proteins with specific functionalities. If enzymes require some flexibility to function properly at their optimal temperatures, it follows that investigation of these structures at other non-native temperatures should reveal a different degree of conformational flexibility. Under such a corresponding states model, homologous mesophilic and thermophilic enzymes should have comparable catalytic efficiencies at their respective optimal temperatures because optimal activity requires a fixed degree of conformational flexibility in the active site. For thermostable enzymes, this catalytically required increase in flexibility only occurs at elevated temperatures upon the loss of local interactions. By logical extension, the remarkable stability of thermophilic enzymes is then a result of these enzymes having an increased conformational rigidity. If enzyme thermostability is dependent upon the underlying structure and its rigidity, then one ought to observe a correspondence between these traits. We hypothesize that the increased stability observed in thermophilic proteins is the result of an increased structural stability. This study investigates the various relationships between thermostability and structural stability. Our results indicate that a large degree of thermostability can be accounted for in terms of rigidity.