3IGK

Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs (p53-DNA complex 2)

Summary for 3IGK

• Entry DOI: 10.2210/pdb3igk/pdb
• Related: 3IGL 3KZ8
• Descriptor: Cellular tumor antigen p53, DNA (5'-D(*CP*GP*GP*GP*CP*AP*TP*GP*CP*CP*CP*G)-3'), ZINC ION, ... (4 entities in total)
• Functional Keywords: p53, mutant protein, loop-sheet-helix motif, dna target, activator, anti-oncogene apoptosis, cell cycle, covalent protein-rna linkage, disease mutation, dna-binding, endoplasmic reticulum, glycoprotein, host-virus interaction, li-fraumeni syndrome, metal-binding, methylation, nucleus, phosphoprotein, transcription, transcription regulation, transcription-dna complex, apoptosis, isopeptide bond, tumor suppressor, transcription/dna
• Biological source: Homo sapiens (human); More
• 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: 2
• Total formula weight: 26184.30

Authors

Suad, O.,Rabinovich, D.,Rozenberg, H.,Shakked, Z. (deposition date: 2009-07-28, release date: 2010-03-31, Last modification date: 2023-11-01)

Primary citation

Kitayner, M.,Rozenberg, H.,Rohs, R.,Suad, O.,Rabinovich, D.,Honig, B.,Shakked, Z.
Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs
Nat.Struct.Mol.Biol., 17:423-429, 2010

PubMed Abstract: p53 binds as a tetramer to DNA targets consisting of two decameric half-sites separated by a variable spacer. Here we present high-resolution crystal structures of complexes between p53 core-domain tetramers and DNA targets consisting of contiguous half-sites. In contrast to previously reported p53-DNA complexes that show standard Watson-Crick base pairs, the newly reported structures show noncanonical Hoogsteen base-pairing geometry at the central A-T doublet of each half-site. Structural and computational analyses show that the Hoogsteen geometry distinctly modulates the B-DNA helix in terms of local shape and electrostatic potential, which, together with the contiguous DNA configuration, results in enhanced protein-DNA and protein-protein interactions compared to noncontiguous half-sites. Our results suggest a mechanism relating spacer length to protein-DNA binding affinity. Our findings also expand the current understanding of protein-DNA recognition and establish the structural and chemical properties of Hoogsteen base pairs as the basis for a novel mode of sequence readout.

PubMed: 20364130
DOI: 10.1038/nsmb.1800

Experimental method

X-RAY DIFFRACTION (1.7 Å)