Structure of the human telomere in K+ solution: a stable basket-type G-quadruplex with only two G-tetrad layers

J Am Chem Soc. 2009 Apr 1;131(12):4301-9. doi: 10.1021/ja807503g.


Previously, it has been reported that human telomeric DNA sequences could adopt in different experimental conditions four different intramolecular G-quadruplexes each involving three G-tetrad layers, namely, Na(+) solution antiparallel-stranded basket form, K(+) crystal parallel-stranded propeller form, K(+) solution (3 + 1) Form 1, and K(+) solution (3 + 1) Form 2. Here we present a new intramolecular G-quadruplex adopted by a four-repeat human telomeric sequence in K(+) solution (Form 3). This structure is a basket-type G-quadruplex with only two G-tetrad layers: loops are successively edgewise, diagonal, and edgewise; glycosidic conformations of guanines are syn x syn x anti x anti around each tetrad. Each strand of the core has both a parallel and an antiparallel adjacent strands; there are one narrow, one wide, and two medium grooves. Despite the presence of only two G-tetrads in the core, this structure is more stable than the three-G-tetrad intramolecular G-quadruplexes previously observed for human telomeric sequences in K(+) solution. Detailed structural elucidation of Form 3 revealed extensive base pairing and stacking in the loops capping both ends of the G-tetrad core, which might explain the high stability of the structure. This novel structure highlights the conformational heterogeneity of human telomeric DNA. It establishes a new folding principle for G-quadruplexes and suggests new loop sequences and structures for targeting in human telomeric DNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circular Dichroism
  • DNA / chemistry
  • G-Quadruplexes*
  • Guanine / chemistry
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Conformation
  • Nucleic Acid Conformation
  • Potassium / chemistry*
  • Spectrophotometry, Ultraviolet
  • Telomere / chemistry*
  • Temperature


  • Guanine
  • DNA
  • Potassium

Associated data

  • PDB/2KF7
  • PDB/2KF8