title: DNA bending by an adenine--thymine tract and its role in gene regulation.
abstract: 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 proteins, we have determined the crystal structure of the high-affinity DNA target of the cancer-associated human papillomavirus E2 protein. The three independent B-DNA molecules of the crystal structure determined at 2.2-A resolution are examples of A-tract-containing helices where the global direction and magnitude of curvature are in accord with solution data, thereby providing insights, at the base pair level, into the mechanism of DNA bending by such sequence motifs. A comparative analysis of E2-DNA conformations with respect to other structural and biochemical studies demonstrates that (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-specific protein-DNA complex, and (ii) differential binding affinity is regulated by the intrinsic structure and deformability encoded in the base sequence of the DNA target.
authors: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: J
authors: J
authors: Hizver
authors: H
authors: H
authors: Rozenberg
authors: F
authors: F
authors: Frolow
authors: D
authors: D
authors: Rabinovich
authors: Z
authors: Z
authors: Shakked
mesh_terms: D000225:Adenine / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D005786:Gene Expression Regulation; D006801:Humans; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009856:Oncogene Proteins, Viral / Q000737:chemistry*; D027383:Papillomaviridae; D011485:Protein Binding; D011487:Protein Conformation; D013941:Thymine / Q000737:chemistry*
chemical_list: D004268:DNA-Binding Proteins; D009856:Oncogene Proteins, Viral; C069102:oncogene protein E2, Human papillomavirus type 18; D004247:DNA; D000225:Adenine; D013941:Thymine