Structural Basis of DNA Recognition by p53 Tetramers
| Autor: | Zippora Shakked, Malka Kitayner, Naama Kessler, Haim Rozenberg, Lihi Shaulov, Tali E. Haran, Dov Rabinovich |
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| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular HMG-box Base pair Apoptosis Biology Crystallography X-Ray Structure-Activity Relationship Neoplasms Protein–DNA interaction Protein Structure Quaternary Molecular Biology Replication protein A Binding Sites DNA clamp Cell Cycle DNA Cell Biology Molecular biology Protein Structure Tertiary Gene Expression Regulation Neoplastic DNA binding site Biophysics DNA supercoil Tumor Suppressor Protein p53 Protein Binding Binding domain |
| Zdroj: | Molecular Cell. 22:741-753 |
| ISSN: | 1097-2765 |
| Popis: | The tumor-suppressor protein p53 is among the most effective of the cell's natural defenses against cancer. In response to cellular stress, p53 binds as a tetramer to diverse DNA targets containing two decameric half-sites, thereby activating the expression of genes involved in cell-cycle arrest or apoptosis. Here we present high-resolution crystal structures of sequence-specific complexes between the core domain of human p53 and different DNA half-sites. In all structures, four p53 molecules self-assemble on two DNA half-sites to form a tetramer that is a dimer of dimers, stabilized by protein-protein and base-stacking interactions. The protein-DNA interface varies as a function of the specific base sequence in correlation with the measured binding affinities of the complexes. The new data establish a structural framework for understanding the mechanisms of specificity, affinity, and cooperativity of DNA binding by p53 and suggest a model for its regulation by regions outside the sequence-specific DNA binding domain. |
| Databáze: | OpenAIRE |
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