Sequence-specific DNA-protein interaction: the lac represser

A model is proposed for lac repressor-lac operator binding which accounts for the tetrameric subunit structure of the lac repressor and for factors involved in the strength, specificity and regulation of repressor-operator interaction. The model employs a π-helix in the amino terminal 25 residues of the lac repressor whereby three tyrosine residues of each subunit intercalate between base pairs of the lac operator. For the outer palindromic sequences of the operator, base specificity is provided by amino acids adjacent to the carboxyl sides of the tyrosine residues of two of the subunits. The inner palindromic sequences which bind the other two subunits form stems of hairpin loops in the operator. Base specificity for these two subunits is provided by amino acids adjacent to the amino sides of the tyrosine residues. In addition to 12 intercalated tyrosine residues, the model provides for a total of at least eight electrostatic interactions and ten sequence-specific hydrogen bonds.