Formation of G-quadruplexes in poly-G sequences: structure of a propeller-type parallel-stranded G-quadruplex formed by a G₁₅ stretch

Biochemistry. 2014 Dec 16;53(49):7718-23. doi: 10.1021/bi500990v. Epub 2014 Dec 1.

Abstract

Poly-G sequences are found in different genomes including human and have the potential to form higher-order structures with various applications. Previously, long poly-G sequences were thought to lead to multiple possible ways of G-quadruplex folding, rendering their structural characterization challenging. Here we investigate the structure of G-quadruplexes formed by poly-G sequences d(TTG(n)T), where n = 12 to 19. Our data show the presence of multiple and/or higher-order G-quadruplex structures in most sequences. Strikingly, NMR spectra of the TTG₁₅T sequence containing a stretch of 15 continuous guanines are exceptionally well-resolved and indicate the formation of a well-defined G-quadruplex structure. The NMR solution structure of this sequence revealed a propeller-type parallel-stranded G-quadruplex containing three G-tetrad layers and three single-guanine propeller loops. The same structure can potentially form anywhere along a long G(n) stretch, making it unique for molecular recognition by other cellular molecules.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circular Dichroism
  • DNA / chemistry*
  • Deoxyguanine Nucleotides / chemistry
  • G-Quadruplexes*
  • Models, Molecular*
  • Molecular Dynamics Simulation
  • Molecular Weight
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleic Acid Conformation
  • Nucleic Acid Denaturation
  • Polynucleotides / chemistry
  • Solubility
  • Spectrophotometry, Ultraviolet
  • Thymine Nucleotides / chemistry

Substances

  • Deoxyguanine Nucleotides
  • Polynucleotides
  • Thymine Nucleotides
  • DNA