title: Functional interference between contacting amino acids of homeodomains.
abstract: In a protein, the function of an amino acid at some position depends on the amino acids at other positions. Here we demonstrate a functional interference between base-contacting amino acids (at positions 50 and 54) of homeodomains. When, in the context of Antennapedia or Goosecoid homeodomains, Lys50 is paired to Tyr54 or Ala54 and Gln50 is paired to Met54, the resulting proteins efficiently discriminate among different DNA sequences. In contrast, in the presence of the pair Lys50-Met54, both homeodomains show a reduced capability to discriminate among different DNA sequences. Sequence selection experiments performed in the context of the Goosecoid homeodomain suggest that the presence of Met54 precludes the base-discriminating function of Lys50. These results may explain why the pair Lys50-Met54 is never found in natural homeodomains.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pellizzari
authors.forename: G
authors.initials: G
authors.lastname: Tell
authors.forename: D
authors.initials: D
authors.lastname: Fabbro
authors.forename: C
authors.initials: C
authors.lastname: Pucillo
authors.forename: G
authors.initials: G
authors.lastname: Damante
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051943:Antennapedia Homeodomain Protein; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002417:Cattle; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051956:Goosecoid Protein; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D012097:Repressor Proteins; D014157:Transcription Factors
chemical_list: D051943:Antennapedia Homeodomain Protein; D004268:DNA-Binding Proteins; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA