Role of conservative mutations in protein multi-property adaptation
Résumé
Protein physicochemical properties must undergo complex changes during evolution, as a response to modifications in the organism environment, as a result of the proteins taking up new roles or because of the need to cope with the evolution of molecular interacting partners. Recent work has emphasized the role of stability and stability/function trade-offs in these protein adaptation processes. Here, on the other hand, we report that combinations of a few conservative, high-frequency-of-fixation mutations in the thioredoxin molecule lead to largely independent changes in both, stability and the diversity of catalytic mechanisms revealed by single-molecule atomic-force spectroscopy. Furthermore, the changes found are evolutionary significant, as they combine typically hyperthermophilic stability enhancements with modulations in function that span the ranges defined by the quite different catalytic patterns of thioredoxins from bacterial and eukaryotic origin. These results suggest that evolutionary protein adaptation may use, in some cases at least, a potential of conservative mutations to originate a multiplicity of evolutionary-allowed mutational paths leading to a variety of protein modulation patterns. Besides, they support the feasibility of using of evolutionary information to achieve protein multi-feature optimization, an important biotechnological goal.
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