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Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs.

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.

journal_name

Nat Struct Mol Biol

journal_title

Nature structural & molecular biology

authors

Kitayner M,Rozenberg H,Rohs R,Suad O,Rabinovich D,Honig B,Shakked Z

doi

10.1038/nsmb.1800

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

423-9

issue

4

eissn

1545-9993

issn

1545-9985

pii

nsmb.1800

journal_volume

17

pub_type

杂志文章

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