title: In the TTF-1 homeodomain the contribution of several amino acids to DNA recognition depends on the bound sequence.
abstract: The thyroid transcription factor-1 homeodomain (TTF-1HD) shows a peculiar DNA binding specificity, preferentially recognizing sequences containing the 5'-CAAG-3' core motif. Most other homeodomains instead recognize sites containing the 5'-TAAT-3' core motif. Here, we show that TTF-1HD efficiently recognizes another sequence, called D1, devoid of the 5'-CAAG-3' core motif. Different experimental approaches indicate that TTF-1HD contacts the D1 sequence in a manner which is different to that used to interact with sequences containing the 5'-CAAG-3' core motif. The binding activities that mutants of TTF-1HD display with the D1 sequence or with the sequence containing the 5'-CAAG-3' core motif indicate that the role of several DNA-contacting amino acids is different. In particular, during recognition of the D1 sequence, backbone-interacting amino acids not relevant in binding to sequences containing the 5'-CAAG-3' core motif play an important role. In the TTF-1HD, therefore, the contribution of several amino acids to DNA recognition depends on the bound sequence. These data indicate that although a common bonding network exists in all of the HD/DNA complexes, peculiarities important for DNA recognition may occur in single cases.
authors.forename: D
authors.initials: D
authors.lastname: Fabbro
authors.forename: G
authors.initials: G
authors.lastname: Tell
authors.forename: A
authors.initials: A
authors.lastname: Leonardi
authors.forename: L
authors.initials: L
authors.lastname: Pellizzari
authors.forename: C
authors.initials: C
authors.lastname: Pucillo
authors.forename: R
authors.initials: R
authors.lastname: Lonigro
authors.forename: S
authors.initials: S
authors.lastname: Formisano
authors.forename: G
authors.initials: G
authors.lastname: Damante
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001665:Binding Sites; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D019175:DNA Methylation; D018398:Homeodomain Proteins / Q000378:metabolism*; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D004247:DNA