title: Reversal of halophilicity in a protein-DNA interaction by limited mutation strategy.
abstract: Comparison of the genes of functionally homologous proteins in organisms existing in different environments shows that adaptation is most often accomplished by mutation of an existing protein. However, from such comparisons, the significance of individual residues to the particular environmental adaptation is not generally discernable among the mass of changes that occur over evolutionary time. This can be exemplified by the general transcription factor found in eukaryotes and archaea, the TATA binding protein (TBP). TBP from Pyrococcus woesei is adapted for optimal binding to DNA at high salt and high temperature, with 34% of the amino acids altered in comparison to its nearest known mesophilic counterpart. We demonstrate that the halophilic nature of this protein can be attributed to only three mutations, revealing that the important phenotype of halophilicity could be rapidly acquired in evolutionary time.
authors.affiliation: Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Bergqvist
authors.forename: Mark A
authors.initials: MA
authors.lastname: Williams
authors.forename: Ronan
authors.initials: R
authors.lastname: O'Brien
authors.forename: John E
authors.initials: JE
authors.lastname: Ladbury
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019843:Archaeal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002151:Calorimetry; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D019711:Pyrococcus / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D012965:Sodium Chloride / Q000737:chemistry / Q000378:metabolism*; D035181:TATA-Box Binding Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D013696:Temperature
chemical_list: D019843:Archaeal Proteins; D035181:TATA-Box Binding Protein; D012965:Sodium Chloride; D004247:DNA