2ahi
From Proteopedia
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Structural Basis of DNA Recognition by p53 Tetramers (complex III)
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Adrenal cortical carcinoma OMIM:[191170], Breast cancer OMIM:[191170], Colorectal cancer OMIM:[191170], Hepatocellular carcinoma OMIM:[191170], Histiocytoma OMIM:[191170], Li-Fraumeni syndrome OMIM:[191170], Multiple malignancy syndrome OMIM:[191170], Nasopharyngeal carcinoma OMIM:[191170], Osteosarcoma OMIM:[191170], Pancreatic cancer OMIM:[191170], Thyroid carcinoma OMIM:[191170]
About this Structure
2AHI is a Single protein structure of sequence from Homo sapiens with ZN as ligand. Full crystallographic information is available from OCA.
Reference
Structural basis of DNA recognition by p53 tetramers., Kitayner M, Rozenberg H, Kessler N, Rabinovich D, Shaulov L, Haran TE, Shakked Z, Mol Cell. 2006 Jun 23;22(6):741-53. PMID:16793544
Page seeded by OCA on Mon Nov 12 20:51:21 2007
