Solution structure of an A-tract DNA bend

MacDonald, Douglas; Herbert, Kristina M.; Zhang, X; Pologruto, T; Lü, Peng

doi:10.1006/jmbi.2001.4447

Cited by 146 publications

(115 citation statements)

References 76 publications

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“…Because roll and tilt have several positive and negative components of relatively small magnitudes that all contribute to the bend, we call this the delocalized bend (DB) model. This DB model is also supported by a recent NMR structure of an A 6 -tract (A6) (42). Using our structure analysis methodology (3DNA͞MADBEND), we find the inner 10 bp of this dodecamer to be bent by 15.7°into the minor groove between the third and fourth A⅐T base pairs.…”

Section: Discussionsupporting

confidence: 81%

Structural origins of adenine-tract bending

Barbič

Zimmer

Crothers

2003

Proc. Natl. Acad. Sci. U.S.A.

110

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DNA sequences containing short adenine tracts are intrinsically curved and play a role in transcriptional regulation. Despite many high-resolution NMR and x-ray studies, the origins of curvature remain disputed. Long-range restraints provided by 85 residual dipolar couplings were measured for a DNA decamer containing an adenine (A) 4-tract and used to refine the structure. The overall bend in the molecule is a result of in-phase negative roll in the A-tract and positive roll at its 5 junction, as well as positive and negative tilt inside the A-tract and near its junctions. The bend magnitude and direction obtained from NMR structures is 9.0°into the minor groove in a coordinate frame located at the third AT base pair. We evaluated long-range and wedge models for DNA curvature and concluded that our data for A-tract curvature are best explained by a ''delocalized bend'' model. The global bend magnitude and direction of the NMR structure are in excellent agreement with the junction model parameters used to rationalize gel electrophoretic data and with preliminary results of a cyclization kinetics assay from our laboratory. I t has been known for Ϸ20 years that DNA molecules containing four to six consecutive adenine-thymine base pairs exhibit intrinsic curvature (1). This curvature can play a significant role in transcriptional activation by affecting promoter geometry. Many transcriptional activators are DNA-bending proteins that can either recognize DNA bases (direct recognition) or specific DNA properties such as flexibility (indirect recognition) (2). Escherichia coli promoters frequently contain an adenine (A)-tract region, mostly centered around the Ϫ44 region, which when mutated has been shown to reduce transcription (3). In some cases, substitution of an entire promoter region by properly curved DNA can activate in vitro transcription (4, 5). More recent work indicates that these sequences function as upstream recognition elements (UP elements), the curvatures of which play an unknown role (6). In addition, HIV-1 reverse transcriptase termination of the (ϩ) strand DNA synthesis is thought to occur because of minor groove compression of duplex DNA caused by the A-tracts (7,8). Understanding A-tract geometry can therefore play an important role in our understanding of gene expression. Despite many structural efforts, no consensus about the stereochemical origins of the bend has yet emerged. A-tract molecules studied by x-ray crystallography are all bent in directions orthogonal to that established by gel and solution studies (1). Solution NMR, which is not prone to the artifacts of the crystal environment, has only recently been able to provide the long-range restraints necessary to determine global DNA properties (9). We present application of dipolar couplings to determination of DNA bending of an A 4 -tract and discuss implications for DNA-bending models and stereochemical origins of curvature. Because reliable values for the magnitude and direction of DNA bends can be obtained by cyclization kinetics (10...

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Section: Discussionsupporting

confidence: 81%

Structural origins of adenine-tract bending

Barbič

Zimmer

Crothers

2003

Proc. Natl. Acad. Sci. U.S.A.

110

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“…Molecular dynamics (35), NMR (10), and X-ray crystal structure (44) studies of A tract-containing sequences have indicated that the observed bending is a consequence of A tract and non-A tract regions of the sequence. Consequently, the length of the cooperative unit for the A 3 T 3 duplex is not defined, and we prefer to consider the energetics of premelting and the three-centered H-bond in terms of the number of A‚T base pairs and A-A base steps (Table 2).…”

Section: Discussionmentioning

confidence: 99%

“…NMR characterization of a DNA duplex containing an A 3 T 3 1 tract detected elevated activation enthalpies and entropies of amino group rotation for the central A5 residue, consistent with the formation of a threecentered H-bond (9). More recently, an NMR structural determination of an A tract-containing sequence has also yielded interstrand distances indicative of bifurcated H-bond formation (10).…”

mentioning

confidence: 99%

UV Resonance Raman and Circular Dichroism Studies of a DNA Duplex Containing an A₃T₃ Tract: Evidence for a Premelting Transition and Three-Centered H-Bonds

Mukerji

Williams

2001

Biochemistry

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The presence of A n and A n T n tracts in double-helical sequences perturbs the structural properties of DNA molecules, resulting in the formation of an alternate conformation to standard B-DNA known as B‘-DNA. Evidence for a transition occurring prior to duplex melting in molecules containing A n tracts was previously detected by circular dichroism (CD) and calorimetric studies. This premelting transition was attributed to a conformational change from B‘- to B-DNA. Structural features of A n and A n T n tracts revealed by X-ray crystallography include a large degree of propeller twisting of adenine bases, narrowed minor grooves, and the formation of three-centered H-bonds between dA and dT bases. We report UV resonance Raman (UVRR) and CD spectroscopic studies of two related DNA dodecamer duplexes, d(CGCAAATTTGCG)2 (A3T3) and d(CGCATATATGCG)2 [(AT)3]. These studies address the presence of three-centered H-bonds in the B‘ conformation and gauge the impact of these putative H-bonds on the structural and thermodynamic properties of the A3T3 duplex. UVRR and CD spectra reveal that the premelting transition is only observed for the A3T3 duplex, is primarily localized to the dA and dT bases, and is associated with base stacking interactions. Spectroscopic changes associated with the premelting transition are not readily detectable for the sugar−phosphate backbone or the cytosine and guanosine bases. The temperature-dependent concerted frequency shifts of dA exocyclic NH2 and dT C4O vibrational modes suggest that the A3T3 duplex forms three-centered hydrogen bonds at low temperatures, while the (AT)3 duplex does not. The enthalpy of this H-bond, estimated from the thermally induced frequency shift of the dT C4O vibrational mode, is approximately 1.9 kJ/mol or 0.46 kcal/mol.

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“…The high positive or negative rolls of the TpA and ApT steps (discussed above), respectively, probably suppress the propeller twist around the central (TpA or ApT) steps relative to the outer parts of A-blocks (ϷϪ16°for A4T4 and Ϫ17°f or T4A4) ( Table 2). High propeller twists in A-tracts have been observed in all crystal structures and also in an NMR structure solved with RDCs (21), resulting in A-tract bifurcated hydrogen bonds in the major groove, and have been associated with the compression of the minor groove (13,14,17,21). However, in a recently published A-tract structure determined by NMR with RDCs (22), neither A-tract minor groove compression nor bending was found to structurally depend on high propeller twisting.…”

Section: Comparison To Related Solution and Crystal Structuresmentioning

confidence: 98%

“…High-resolution structure determination of DNA by NMR has been limited both by the relatively low number of short-range restraints that determine the local dinucleotide structure and, until recently, by lack of long-range (Ͼ7 Å) restraints for the accurate determination of the global bend. The application of residual dipolar couplings (RDCs) (19) has in principle made it possible to get accurate long-range angular information for DNA helices, and several recent studies have used them (20)(21)(22). Both x-ray and solution structural analysis of A-tract bending have also been limited by the short DNA length (usually only one helical turn) and end effects.…”

mentioning

confidence: 99%

DNA A-tract bending in three dimensions: Solving the dA ₄ T ₄ vs. dT ₄ A ₄ conundrum

Štefl

Ravindranathan

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

138

143

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Solution structure of an A-tract DNA bend

Cited by 146 publications

References 76 publications

Structural origins of adenine-tract bending

Structural origins of adenine-tract bending

UV Resonance Raman and Circular Dichroism Studies of a DNA Duplex Containing an A₃T₃ Tract: Evidence for a Premelting Transition and Three-Centered H-Bonds

DNA A-tract bending in three dimensions: Solving the dA ₄ T ₄ vs. dT ₄ A ₄ conundrum

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Solution structure of an A-tract DNA bend

Cited by 146 publications

References 76 publications

Structural origins of adenine-tract bending

Structural origins of adenine-tract bending

UV Resonance Raman and Circular Dichroism Studies of a DNA Duplex Containing an A3T3 Tract: Evidence for a Premelting Transition and Three-Centered H-Bonds

DNA A-tract bending in three dimensions: Solving the dA 4 T 4 vs. dT 4 A 4 conundrum

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UV Resonance Raman and Circular Dichroism Studies of a DNA Duplex Containing an A₃T₃ Tract: Evidence for a Premelting Transition and Three-Centered H-Bonds

DNA A-tract bending in three dimensions: Solving the dA ₄ T ₄ vs. dT ₄ A ₄ conundrum