Functional interference between contacting amino acids of homeodomains

• Published in: FEBS letters 1997-05, Vol.407 (3), p.320-324
• Main Authors: Pellizzari, Lucia, Tell, Gianluca, Fabbro, Dora, Pucillo, Carlo, Damante, Giuseppe
• Format: Article
• Language: English
• Subjects: Amino acid; Amino Acid Sequence; Animals; Antennapedia Homeodomain Protein; Base Sequence; Binding Sites - genetics; Cattle; DNA - genetics; DNA - metabolism; DNA binding; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Goosecoid Protein; Homeodomain; Homeodomain Proteins - chemistry; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; In Vitro Techniques; Molecular Sequence Data; Nuclear Proteins; Oligodeoxyribonucleotides - genetics; Repressor Proteins; Transcription Factors
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(97)00368-2

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, Lys 50 is paired to Tyr 54 or Ala 54 and Gln 50 is paired to Met 54, the resulting proteins efficiently discriminate among different DNA sequences. In contrast, in the presence of the pair Lys 50-Met 54, 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 Met 54 precludes the base-discriminating function of Lys 50. These results may explain why the pair Lys 50-Met 54 is never found in natural homeodomains.