We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs.
- Authors
Kitayner, Malka; Rozenberg, Haim; Rohs, Remo; Suad, Oded; Rabinovich, Dov; Honig, Barry; Shakked, Zippora
- 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.
- Subjects
DNA; PROTEIN-protein interactions; MOLECULAR association; PROTEIN binding; BIOCHEMISTRY
- Publication
Nature Structural & Molecular Biology, 2010, Vol 17, Issue 4, p423
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.1800