Structural basis for DNA bending.

Nadeau, James G.; Crothers, Donald M.

doi:10.1073/pnas.86.8.2622

Cited by 144 publications

(146 citation statements)

References 31 publications

(56 reference statements)

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“…37,38 Overall, the complex displays a narrow minor groove and a large negative propeller twist, which are features typically associated with A-tract structures. 39 The narrow minor groove is confirmed by the observation of medium-intensity cross-strand NOEs (type a distance 31 ) between each adenine H2 and H1 0 of its base-paired thymidine's 3 0 -neighbor (red stars in Figure 4). The minor groove in the structural ensemble is much narrower than observed for ligand-free duplex DNA containing similar sequences-5 0 -AAAGAA-3 0 by NMR 40 as well as 5 0 -AAAGAAAA-3 0 and short A-tracts by X-ray crystallography.…”

Section: Overall Featuresmentioning

confidence: 72%

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Structure of a β-Alanine-linked Polyamide Bound to a Full Helical Turn of Purine Tract DNA in the 1:1 Motif

Urbach

Love

Ross

et al. 2002

Journal of Molecular Biology

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Polyamides composed of N-methylpyrrole (Py), N-methylimidazole (Im) and N-methylhydroxypyrrole (Hp) amino acids linked by b-alanine (b) bind the minor groove of DNA in 1:1 and 2:1 ligand to DNA stoichiometries. Although the energetics and structure of the 2:1 complex has been explored extensively, there is remarkably less understood about 1:1 recognition beyond the initial studies on netropsin and distamycin. We present here the 1:1 solution structure of ImPy -b -Im-b -ImPy -b-Dp bound in a single orientation to its match site within the DNA duplex 5 0 -CCAAAGAGAAGCG-3 0 ·5 0 -CGCTTCTCTTTGG-3 0 (match site in bold), as determined by 2D 1 H NMR methods. The representative ensemble of 12 conformers has no distance constraint violations greater than 0.13 Å and a pairwise RMSD over the binding site of 0.80 Å . Intermolecular NOEs place the polyamide deep inside the minor groove, and oriented N -C with the 3 0 -5 0 direction of the purine-rich strand. Analysis of the high-resolution structure reveals the ligand bound 1:1 completely within the minor groove for a full turn of the DNA helix. The DNA is B-form (average rise ¼ 3.3 Å , twist ¼ 388) with a narrow minor groove closing down to 3.0-4.5 Å in the binding site. The ligand and DNA are aligned in register, with each polyamide NH group forming bifurcated hydrogen bonds of similar length to purine N3 and pyrimidine O2 atoms on the floor of the minor groove. Each imidazole group is hydrogen bonded via its N3 atom to its proximal guanine's exocyclic amino group. The important roles of b-alanine and imidazole for 1:1 binding are discussed.

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Section: Overall Featuresmentioning

confidence: 72%

“…This pattern is indicative of a narrow minor groove. 31 The nomenclature for polyamide protons is shown in Figure 1. All polyamide protons were assigned.…”

Section: Spectral Assignmentsmentioning

confidence: 99%

Structure of a β-Alanine-linked Polyamide Bound to a Full Helical Turn of Purine Tract DNA in the 1:1 Motif

Urbach

Love

Ross

et al. 2002

Journal of Molecular Biology

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“…2B); and in synthetic curved DNA molecules (data not shown). These A tract motifs are related to the junction model, in which the deflection of the helix axis is localized at junctions between BЈ form structure of A tracts and B form (29). Furthermore, all regions stably bound by LrpC contained phased A tracts preceded by a C (i.e.…”

Section: Fig 4 Identification Of a Curved Region Of Pbr322 To Whichmentioning

confidence: 99%

Contribution of DNA Conformation and Topology in Right-handed DNA Wrapping by the Bacillus subtilis LrpC Protein

Beloin¹,

Jeusset²,

Révet³

et al. 2003

Journal of Biological Chemistry

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The Bacillus subtilis LrpC protein belongs to the Lrp/ AsnC family of transcriptional regulators. It binds the upstream region of the lrpC gene and autoregulates its expression. In this study, we have dissected the mechanisms that govern the interaction of LrpC with DNA by electrophoretic mobility shift assay, electron microscopy, and atomic force microscopy. LrpC is a structurespecific DNA binding protein that forms stable complexes with curved sequences containing phased A tracts and wraps DNA to form spherical, nucleosomelike structures. Formation of such wraps, initiated by cooperative binding of LrpC to DNA, results from optimal protein/protein interactions specified by the DNA conformation. In addition, we have demonstrated that LrpC constrains positive supercoils by wrapping the DNA in a right-handed superhelix, as visualized by electron microscopy.

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“…The stability of the complex depends on many factors including the DNA sequence (36), the length of the DNA segment, whether full-length p53 protein or its core domains were involved, and possibly the conformational changes within the p53 monomer. The fact that full-length p53 can trigger a larger extent of DNA bending clearly demonstrates the involvement of other protein parts in maintaining the stability of the bent DNA.…”

Section: Dna Intrinsic Properties and Conformational Changes Upon P53mentioning

confidence: 99%

Structural Basis for p53 Binding-induced DNA Bending

Pan

Nussinov

2007

Journal of Biological Chemistry

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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°, 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.

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Structural basis for DNA bending.

Cited by 144 publications

References 31 publications

Structure of a β-Alanine-linked Polyamide Bound to a Full Helical Turn of Purine Tract DNA in the 1:1 Motif

Structure of a β-Alanine-linked Polyamide Bound to a Full Helical Turn of Purine Tract DNA in the 1:1 Motif

Contribution of DNA Conformation and Topology in Right-handed DNA Wrapping by the Bacillus subtilis LrpC Protein

Structural Basis for p53 Binding-induced DNA Bending

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