MECHANISM OF LAC REPRESSOR SWITCH-OFF - ORIENTATION OF THE LAC REPRESSOR DNA-BINDING DOMAIN IS REVERSED UPON INDUCER BINDING

Lac repressor's DNA-binding domains contain helix-turn-helix motif whi ch, though similar to those of phage lambda Cro protein, are oriented differently with respect to DNA: in the specific complexes with Lac op erator, N termini of the repressor's subunits are facing inwards, We d emonstrate that, in the presence of an inducer, the repressor's N term ini cross-link to the operator's outermost nucleotides. We suggest tha t the inducer fixes the repressor's DNA-binding domains in the Cro-typ e configuration and thus garbles its recognition surface, Since the Cr o-type configuration is perfectly suitable for binding the DNA, this a lso explains how the switched-off repressor retains its nonspecific DN A-binding.