2AHI

Structural Basis of DNA Recognition by p53 Tetramers (complex III)

Summary for 2AHI

• Entry DOI: 10.2210/pdb2ahi/pdb
• Related: 2AC0 2ADY 2ATA
• Descriptor: 5'-D(*CP*GP*GP*AP*CP*AP*TP*GP*TP*CP*CP*G)-3', Cellular tumor antigen p53, ZINC ION, ... (4 entities in total)
• Functional Keywords: protein-dna complex, apoptosis-dna complex, apoptosis/dna
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637
• Total number of polymer chains: 8
• Total formula weight: 104937.53

Authors

Kitayner, M.,Rozenberg, H.,Kessler, N.,Rabinovich, D.,Shakked, Z. (deposition date: 2005-07-28, release date: 2006-07-11, Last modification date: 2023-10-25)

Primary citation

Kitayner, M.,Rozenberg, H.,Kessler, N.,Rabinovich, D.,Shaulov, L.,Haran, T.E.,Shakked, Z.
Structural Basis of DNA Recognition by p53 Tetramers
Mol.Cell, 22:741-753, 2006

PubMed Abstract: 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.

PubMed: 16793544
DOI: 10.1016/j.molcel.2006.05.015

Experimental method

X-RAY DIFFRACTION (1.85 Å)