title: Role of conservative mutations in protein multi-property adaptation.
abstract: Protein physicochemical properties must undergo complex changes during evolution, as a response to modifications in the organism environment, the 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. In the present study, 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, as revealed by single-molecule atomic force spectroscopy. Furthermore, the changes found are evolutionarily 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, the potential of conservative mutations to originate a multiplicity of evolutionarily allowed mutational paths leading to a variety of protein modulation patterns. In addition the results support the feasibility of using evolutionary information to achieve protein multi-feature optimization, an important biotechnological goal.
authors.affiliation: Departamento de Quimica Fisica, Facultad de Ciencias, Universidad de Granada, 18071-Granada, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Rodriguez-Larrea
authors.forename: Raul
authors.initials: R
authors.lastname: Perez-Jimenez
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Sanchez-Romero
authors.forename: Asuncion
authors.initials: A
authors.lastname: Delgado-Delgado
authors.forename: Julio M
authors.initials: JM
authors.lastname: Fernandez
authors.forename: Jose M
authors.initials: JM
authors.lastname: Sanchez-Ruiz
mesh_terms: D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D007700:Kinetics; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D013879:Thioredoxins / Q000737:chemistry / Q000235:genetics / Q000502:physiology
chemical_list: D029968:Escherichia coli Proteins; D011506:Proteins; D013879:Thioredoxins
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