Gradual adaptive changes of a protein facing high salt concentrations.
Several experimental techniques were applied to unravel fine molecular details of protein adaptation to high salinity. We compared four homologous enzymes, which suggested a new halo-adaptive state in the process of molecular adaptation to high-salt conditions. Together with comparative functional studies, the structure of malate dehydrogenase from the eubacterium Salinibacter ruber shows that the enzyme shares characteristics of a halo-adapted archaea-bacterial enzyme and of non-halo-adapted enzymes from other eubacterial species. The S. ruber enzyme is active at the high physiological concentrations of KCl but, unlike typical halo-adapted enzymes, remains folded and active at low salt concentrations. Structural aspects of the protein, including acidic residues at the surface, solvent-exposed hydrophobic surface, and buried hydrophobic surface, place it between the typical halo-adapted and non-halo-adapted proteins. The enzyme lacks inter-subunit ion-binding sites often seen in halo-adapted enzymes. These observations permit us to suggest an evolutionary pathway that is highlighted by subtle trade-offs to achieve an optimal compromise among solubility, stability, and catalytic activity.
Coquelle
Nicolas
N
IBS, Institut de Biologie Structurale Jean-Pierre Ébel, Extremophilic and Large Molecular Assemblies Team, UMR 5075, CEA, CNRS, Université Joseph Fourier, 41 rue Jules Horowitz, F-38027 Grenoble, France.
Talon
Romain
R
Juers
Douglas H
DH
Girard
Eric
E
Kahn
Richard
R
Madern
Dominique
D
D019843:Archaeal Proteins / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D041963:Bacteroidetes / Q000201:enzymology*; D020134:Catalytic Domain; D041861:Chloroflexus / Q000201:enzymology; D018360:Crystallography, X-Ray; D004795:Enzyme Stability / Q000187:drug effects; D019614:Haloarcula marismortui / Q000201:enzymology; D057927:Hydrophobic and Hydrophilic Interactions; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011189:Potassium Chloride / Q000494:pharmacology; D011487:Protein Conformation / Q000187:drug effects; D020836:Protein Structure, Quaternary; D054712:Salinity; D012995:Solubility / Q000187:drug effects; D013045:Species Specificity; D016963:Thermus thermophilus / Q000201:enzymology
D019843:Archaeal Proteins; D001426:Bacterial Proteins; D011189:Potassium Chloride; D007770:L-Lactate Dehydrogenase; D008291:Malate Dehydrogenase