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Solution structure of a parallel-stranded G-quadruplex DNA

Y Wang1, D J Patel

  • 1Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032.

Journal of Molecular Biology
|December 20, 1993
PubMed
Summary
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This study reveals the parallel-stranded G-quadruplex structure of the Tetrahymena telomeric sequence using NMR and computational methods. The G-quadruplex exhibits 4-fold symmetry with stacked G.G.G.G tetrads, offering insights into telomere structure.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Biophysics

Background:

  • G-quadruplexes are nucleic acid structures implicated in telomere maintenance and gene regulation.
  • The Tetrahymena telomeric sequence forms a parallel-stranded G-quadruplex structure.
  • Understanding G-quadruplex structure is crucial for developing therapeutic strategies.

Purpose of the Study:

  • To determine the high-resolution solution structure of the parallel-stranded G-quadruplex formed by the Tetrahymena telomeric sequence d(T-T-G-G-G-G-T).
  • To elucidate the structural features and stability of this G-quadruplex in a potassium-containing solution.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy to obtain structural parameters.
  • Quantitative analysis of NMR data combined with molecular dynamics (MD) calculations.

Related Experiment Videos

  • Relaxation matrix refinement and distance-refined structure calculations.

    • Main Results:

    • A parallel-stranded G-quadruplex structure with approximate 4-fold symmetry was determined.
    • The structure features stacked G.G.G.G tetrads, each stabilized by eight hydrogen bonds.
    • All guanines adopted anti glycosidic torsion angles and S-type sugar pucker in a right-handed helix.
    • Thymine residues showed conformational flexibility.

    Conclusions:

    • The study provides a detailed atomic model of the Tetrahymena telomeric G-quadruplex in solution.
    • The findings contribute to understanding the structural diversity and stability of G-quadruplexes.
    • This structural information can inform the design of G-quadruplex-targeting agents.