PDBsum entry 1a6h

DNA

PDB id

1a6h

Contents

			DNA/RNA

References listed in PDB file

Key reference

Title

Solution structure of a DNA quadruplex containing the fragile x syndrome triplet repeat.

Authors

A.Kettani, R.A.Kumar, D.J.Patel.

Ref.

J Mol Biol, 1995, 254, 638-656. [DOI no: 10.1006/jmbi.1995.0644]

PubMed id

7500339

Abstract

Both X-ray and NMR structural studies have defined the polymorphic nature of G-quadruplexes generated through mutual stacking of G.G.G.G tetrads by guanine rich telomeric sequences. Recently, the fragile X syndrome d(C-G-G)n triplet nucleotide repeat has been shown to form a stable quadruplex of undefined structure in monovalent cation solution. We have undertaken a structural characterization of the d(G-C-G-G-T3-G-C-G-G) undecanucleotide to elucidate the structural alignments associated with quadruplex formation by this oligomer which contains sequence elements associated with the fragile X syndrome triplet repeat. d(G-C-G-G-T3-G-C-G-G) in Na+ cation solution forms a quadruplex through dimerization of two symmetry related hairpins with the lateral connecting T3 loops positioned at opposite ends of the quadruplex. This novel NMR-molecular dynamics based solution structure contains internal G.C.G.C tetrads sandwiched between terminal G.G.G.G tetrads. Watson-Crick G.C base-pairs within individual hairpins dimerize through their major groove edges using bifurcated hydrogen bonds to form internal G(anti).C(anti).G(anti).C(anti) tetrads. Adjacent strands are anti-parallel to each other around the symmetric G-quadruplex which contains two distinct narrow and two symmetric wide grooves. By contrast, the terminal G-tetrads adopt G(syn).G(anti).G(syn).G(anti) alignments. The structure of the d(G-C-G-G-T3-G-C-G-G) quadruplex with its multi-layer arrangement of G.G.G.G and G.C.G.C tetrads greatly expands on our current knowledge of quadruplex folding topologies. Our results establish the pairing alignments that can be potentially utilized by the fragile X syndrome triplet repeat to form quadruplex structures through dimerization of hairpin stems. The formation of novel G.C.G.C tetrads through dimerization of Watson-Crick G.C base-pairs is directly relevant to the potential pairing alignments of helical stems in genetic recombination.



	Figure 2. Figure 2. Schematic diagram showing the folding topology of the d(G-C-G-G-T3-G-C-G-G) quadruplex in Na + containing solution. The backbone tracing of individual hairpins is shown by thick lines and the chain directionality by thick arrows. Hydrogen bonding donor to acceptor directionalities around individual G·G·G·G tetrads are represented by arrows as are Watson-Crick G·C pairs within G·C·G·C tetrads. Syn guanine residues are shaded to distinguish them from anti guanine residues. The two distinct inter-strand narrow grooves are labelled N1 and N2 while the symmetric intra-strand wide grooves are labelled W.		Figure 9. Figure 9. Views normal to the helix axis and looking (a) into the narrow N2 groove and (b) into the wide groove in the representative relaxation matrix refined structure of the d(G-C-G-G-T3-G-C-G-G) quadruplex. View generated using the ``stick'' representation (INSIGHT II program). The G1-C2-G3-G4 segments are shown in green and cyan, the T5-T6-T7 segments are shown in white and the G8-C9-G10-G11 segments are shown in magenta and yellow. All hydrogen atoms and phosphate oxygen atoms in the backbone have been deleted for clarity.

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