DNA bending by an adenine-thymine tract and its role in gene regulation

To gain insight into the structural basis of DNA bending by adenine-thymine tracts (A-tracts) and their role in DNA recognition by gene-regulatory pro teins, we have determined the crystal structure of the high-affinity DNA ta rget of the cancer-associated human papillomavirus E2 protein. The three in dependent B-DNA molecules of the crystal structure determined at 2.2-Angstr om resolution are examples of A-tract-containing helices where the global d irection and magnitude of curvature are in accord with solution data, there by providing insights, at the base pair level, into the mechanism of DNA be nding by such sequence motifs, A comparative analysis of E2-DNA conformatio ns with respect to other structural and biochemical studies demonstrates th at (i) the A-tract structure of the core region, which is not contacted by the protein, is critical for the formation of the high-affinity sequence-sp ecific protein-DNA complex, and (ii) differential binding affinity is regul ated by the intrinsic structure and deformability encoded in the base seque nce of the DNA target.