3IGL: Diversity In Dna Recognition By P53 Revealed By Crystal Structures With Hoogsteen Base Pairs (P53-Dna Complex 1)

Citation:
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.
PDB ID: 3IGLDownload
MMDB ID: 81101
PDB Deposition Date: 2009/7/28
Updated in MMDB: 2011/06
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 3IGL: tetrameric; determined by author and by software (PISA)
Molecular Components in 3IGL
Label Count Molecule
Proteins (2 molecules)
2
Cellular Tumor Antigen P53(Gene symbol: TP53)
Molecule annotation
Nucleotide(1 molecule)
2
DNA (5'-d(*cp*gp*gp*gp*cp*ap*tp*gp*cp*cp*cp*g)-3')
Molecule annotation
Chemicals (4 molecules)
1
2
2
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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