Structure and dynamics in Lac repressor-DNA interactions

The E. coli lac operon is the classical model for gene regulation in bacteria. An overview will be given of our work on the lac repressor-operator system. An early result was the 3D structure of lac headpiece in 1985, one of the first protein structures determined by NMR. Our studies of the structure and dynamics of complexes of a dimeric headpiece construct with lac operator DNA have provided a detailed picture of how the various lac operator sequences are recognized. Furthermore, comparison with the non-specific DNA complex clarified how the repressor searches for its target site by sliding along random DNA and binds to the operator through a folding-coupled-to-binding transition. Surprisingly, the 1D diffusion rate obtained from NMR is much slower than that determined by single molecule fluorescence methods and cannot account for an enhanced target location by lac repressor.