FUNCTIONAL INTERFERENCE BETWEEN CONTACTING AMINO-ACIDS OF HOMEODOMAINS

In a protein, the function of an amino acid at some position depends o n 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 Goosecoi d homeodomains, Lys(50) is paired to Tyr(54) or Ala(54) and Gln(50) is paired to Met(54), the resulting proteins efficiently discriminate am ong different DNA sequences. In contrast, in the presence of the pair Lys(50)-Met(54), both homeodomains show a reduced capability to discri minate among different DNA sequences. Sequence selection experiments p erformed 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 f ound in natural homeodomains. (C) 1997 Federation of European Biochemi cal Societies.