Structural basis for p53 binding-induced DNA bending.

Structural basis for p53 binding-induced DNA bending. Research Abstract Details 

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Structural basis for p53 binding-induced DNA bending. Abstract Text:

Yongping Pan,Ruth Nussinov,

Specific p53 binding-induced DNA bending has important biological implications such as transcription activation. However, the detailed structures of the bent DNA and the p53-DNA complex are still unavailable, hampering our understanding of the mechanism for p53-induced DNA bending and its consequent biological significance. To gain insight into the p53 binding-induced DNA bending, we performed molecular dynamics simulations on DNA segments with the consensus sequence for p53-specific binding, half site DNA-p53 complexes, and full site DNA-p53 complexes. We show that each DNA-bound p53 core domain caused a local DNA conformational change within the quarter site; upon the binding of the p53 dimer, there was an apparent DNA bending at the center of the half site; when bound with two p53 dimers, the full site DNAs with two different sequences bent 20 and 35 degrees, respectively. These results are in agreement with experimental observations. Our simulations demonstrate that the two p53 dimers favored a staggered conformation in which they make favorable interactions at the interface. This dimer-dimer interface organization necessitated conformational changes in the DNA, leading to the bending at the center of the full site, which in turn is dependent on the DNA sequence. Overall, our results provide the detailed atomic model for the DNA-p53 tetramer complex and delineate the roles of DNA-p53, p53 dimer-dimer interactions, and DNA sequence in specific p53 binding-induced DNA conformational changes.

Structural basis for p53 binding-induced DNA bending. Publishing Authors By Initials

Y Pan,R Nussinov,

For similar proteins: dna-binding proteins: tumor suppressor protein p53 research abstracts see: proteins: dna-binding proteins: tumor suppressor protein p53 research

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MEDLINE DATE:

Structural basis for p53 binding-induced DNA bending. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 691-9

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 3

MONTH: 11

YEAR: 2006

Structural basis for p53 binding-induced DNA bending. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Structural basis for p53 binding-induced DNA bending. Keywords Mesh Terms:

KEYWORDS: Tumor Suppressor Protein p53

MESH TERMS: metabolism

Chemical & Substance for Abstract: Structural basis for p53 binding-induced DNA bending. Information

Substance Name: DNA

Registry Number: 9007-49-2

Grant and Affiliation Information for Structural basis for p53 binding-induced DNA bending.

AFFILIATION: Center for Cancer Research Nanobiology Program, SAIC-Frederick, Inc., NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA.

Country: United States

AGENCY: United States NCI

GRANT: N01-CO-12400

ACRONYM: CO

MEDLINETA: J Biol Chem

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