Self-association of a DNA loop creates a quadruplex: crystal structure of d(GCATGCT) at 1.8 å resolution (original) (raw)
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A zipper-like duplex in DNA: the crystal structure of d(GCGAAAGCT) at 2.1 å resolution
Structure, 1998
Background: The replication origin of the single-stranded (ss)DNA bacteriophage G4 has been proposed to fold into a hairpin loop containing the sequence GCGAAAGC. This sequence comprises a purine-rich motif (GAAA), which also occurs in conserved repetitive sequences of centromeric DNA. ssDNA analogues of these sequences often show exceptional stability which is associated with hairpin loops or unusual duplexes, and may be important in DNA replication and centromere function. Nuclear magnetic resonance (NMR) studies indicate that the GCGAAAGC sequence forms a hairpin loop in solution, while centromere-like repeats dimerise into unusual duplexes. The factors stabilising these unusual secondary structure elements in ssDNA, however, are poorly understood. Results: The nonamer d(GCGAAAGCT) was crystallised as a bromocytosine derivative in the presence of cobalt hexammine. The crystal structure, solved by the multiple wavelength anomalous dispersion (MAD) method at the bromine K-edge, reveals an unexpected zipper-like motif in the middle of a standard B-DNA duplex. Four central adenines, flanked by two sheared G•A mismatches, are intercalated and stacked on top of each other without any interstrand Watson-Crick base pairing. The cobalt hexammine cation appears to participate only in crystal cohesion. Conclusions: The GAAA consensus sequence can dimerise into a stable zipper-like duplex as well as forming a hairpin loop. The arrangement closes the minor groove and exposes the intercalated, unpaired, adenines to the solvent and DNA-binding proteins. Such a motif, which can transform into a hairpin, should be considered as a structural option in modelling DNA and as a potential binding site, where it could have a role in DNA replication, nuclease resistance, ssDNA genome packaging and centromere function.
Structure of B-DNA with Cations Tethered in the Major Groove † , ‡
Biochemistry, 2005
Here, we describe the 1.6-Å X-ray structure of the DDD (Dickerson-Drew dodecamer), which has been covalently modified by the tethering of four cationic charges. This modified version of the DDD, called here the DDD 4+ , is composed of [d(CGCGAAXXCGCG)] 2 , where X is effectively a thymine residue linked at the 5 position to an n-propyl-amine. The structure was determined from crystals soaked with thallium(I), which has been broadly used as a mimic of K + in X-ray diffraction experiments aimed at determining positions of cations adjacent to nucleic acids. Three of the tethered cations are directed radially out from the DNA. The radially directed tethered cations do not appear to induce structural changes or to displace counterions. One of the tethered cations is directed in the 3′ direction, toward a phosphate group near one end of the duplex. This tethered cation appears to interact electrostatically with the DNA. This interaction is accompanied by changes in helical parameters rise, roll, and twist and by a displacement of the backbone relative to a control oligonucleotide. In addition, these interactions appear to be associated with displacement of counterions from the major groove of the DNA.
A-form Conformational Motifs in Ligand-bound DNA Structures
Journal of Molecular Biology, 2000
Recognition and biochemical processing of DNA requires that proteins and other ligands are able to distinguish their DNA binding sites from other parts of the molecule. In addition to the direct recognition elements embedded in the linear sequence of bases (i.e. hydrogen bonding sites), these molecular agents seemingly sense and/or induce an``indirect'' conformational response in the DNA base-pairs that facilitates close intermolecular ®tting. As part of an effort to decipher this sequence-dependent structural code, we have analyzed the extent of B 3 A conformational conversion at individual base-pair steps in protein and drug-bound DNA crystal complexes. We take advantage of a novel structural parameter, the position of the phosphorus atom in the dimer reference frame, as well as other documented measures of local helical structure, e.g. torsion angles, base-pair step parameters. Our analysis pinpoints ligand-induced conformational changes that are dif®cult to detect from the global perspective used in other studies of DNA structure. The collective data provide new structural details on the conformational pathway connecting A and B-form DNA and illustrate how both proteins and drugs take advantage of the intrinsic conformational mechanics of the double helix. Signi®cantly, the base-pair steps which exhibit pure A-DNA conformations in the crystal complexes follow the scale of A-forming tendencies exhibited by synthetic oligonucleotides in solution and the known polymorphism of synthetic DNA ®bers. Moreover, most crystallographic examples of complete B-to-A deformations occur in complexes of DNA with enzymes that perform cutting or sealing operations at the (O3 H -P) phosphodiester linkage. The B 3 A transformation selectively exposes sugar-phosphate atoms, such as the 3 H -oxygen atom, ordinarily buried within the chain backbone for enzymatic attack. The forced remodeling of DNA to the A-form also provides a mechanism for smoothly bending the double helix, for controlling the widths of the major and minor grooves, and for accessing the minor groove edges of individual base-pairs.
The absence of tertiary interactions in a self-assembled DNA crystal structure
Journal of molecular recognition : JMR, 2012
DNA is a highly effective molecule for controlling nanometer scale structure. The convenience of using DNA lies in the programmability of Watson-Crick base-paired secondary interactions, useful both to design branched molecular motifs, and to connect them through sticky-ended cohesion. Recently, the tensegrity triangle motif has been used to self-assemble 3D crystals whose structures have been determined; sticky ends were reported to be the only intermolecular cohesive elements in those crystals [Zheng J, Birktoft, JJ, Chen Y, Wang T, Sha R, Constantinou PE, Ginell SL, Mao C, Seeman NC. 2009. From Molecular to Macroscopic via the Rational Design of a Self-Assembled 3D DNA Crystal. Nature 461:74-77]. A recent communication [Timsit Y, Varnai P. 2011. Cytosine, the double helix and DNA self-assembly. J. Mol. Recognition 24:137-138]
Four-Stranded DNA Structure Stabilized by a Novel G:C:A:T Tetrad
Journal of the American Chemical Society, 2003
The solution structure of a cyclic oligonucleotide d〈pCGCTCATT〉 has been determined by twodimensional NMR spectroscopy and restrained molecular dynamics. Under the appropriate experimental conditions, this molecule self-associates, forming a symmetric dimer stabilized by four intermolecular Watson-Crick base pairs. The resulting four-stranded structure consists of two G:C:A:T tetrads, formed by facing the minor groove side of the Watson-Crick base-pairs. Most probably, the association of the base-pairs is stabilized by coordinating a Na + cation. This is the first time that this novel G:C:A:T tetrad has been found in an oligonucleotide structure. This observation increases considerably the number of sequences that may adopt a four-stranded architecture. Overall, the three-dimensional structure is similar to those observed previously in other quadruplexes formed by minor groove alignment of Watson-Crick base pairs. This resemblance strongly suggests that we may be observing a general motif for DNA-DNA recognition.
Nucleic Acids Research, 1997
The three-dimensional structure of the hairpin formed by d(ATCCTA-GTTA-TAGGAT) has been determined by means of two-dimensional NMR studies, distance geometry and molecular dynamics calculations. The first and the last residues of the tetraloop of this hairpin form a sheared G-A base pair on top of the six Watson-Crick base pairs in the stem. The glycosidic torsion angles of the guanine and adenine residues in the G-A base pair reside in the anti and high-anti domain (∼-60_) respectively. Several dihedral angles in the loop adopt non-standard values to accommodate this base pair. The first and second residue in the loop are stacked in a more or less normal helical fashion; the fourth loop residue also stacks upon the stem, while the third residue is directed away from the loop region. The loop structure can be classified as a so-called type-I loop, in which the bases at the 5′-end of the loop stack in a continuous fashion. In this situation, loop stability is unlikely to depend heavily on the nature of the unpaired bases in the loop. Moreover, the present study indicates that the influence of the polarity of a closing A·T pair is much less significant than that of a closing C·G base pair.
Biopolymers, 2014
Our previous DFT computations of deoxydinucleoside monophosphate complexes with Na 1-ions (dDMPs) have demonstrated that the main characteristics of Watson-Crick (WC) right-handed duplex families are predefined in the local energy minima of dDMPs. In this work, we study the mechanisms of contribution of chemically monotonous sugar-phosphate backbone and the bases into the double helix irregularity. Geometry optimization of sugar-phosphate backbone produces energy minima matching the WC DNA conformations. Studying the conformational variability of dDMPs in response to sequence permutation, we found that simple replacement of bases
Self-association of short DNA loops through minor groove C:G:G:C tetrads
Nucleic Acids Research, 2009
In addition to the better known guanine-quadruplex, four-stranded nucleic acid structures can be formed by tetrads resulting from the association of Watson-Crick base pairs. When such association occurs through the minor groove side of the base pairs, the resulting structure presents distinctive features, clearly different from quadruplex structures containing planar G-tetrads. Although we have found this unusual DNA motif in a number of cyclic oligonucleotides, this is the first time that this DNA motif is found in linear oligonucleotides in solution, demonstrating that cyclization is not required to stabilize minor groove tetrads in solution. In this article, we have determined the solution structure of two linear octamers of sequence d(TGCTTCGT) and d(TCGTTGCT), and their cyclic analogue d, utilizing 2D NMR spectroscopy and restrained molecular dynamics. These three molecules self-associate forming symmetric dimers stabilized by a novel kind of minor groove C:G:G:C tetrad, in which the pattern of hydrogen bonds differs from previously reported ones. We hypothesize that these quadruplex structures can be formed by many different DNA sequences, but its observation in linear oligonucleotides is usually hampered by competing Watson-Crick duplexes.