Reversible pH Switch of Two-Quartet G-Quadruplexes Formed by Human Telomere

Angew Chem Int Ed Engl. 2016 Feb 5;55(6):1993-7. doi: 10.1002/anie.201507569. Epub 2016 Jan 6.

Abstract

A four-repeat human telomere DNA sequence without the 3'-end guanine, d[TAGGG(TTAGGG)2 TTAGG] (htel1-ΔG23) has been found to adopt two distinct two G-quartet antiparallel basket-type G-quadruplexes, TD and KDH(+) in presence of KCl. NMR, CD, and UV spectroscopy have demonstrated that topology of KDH(+) form is distinctive with unique protonated T18⋅A20(+) ⋅G5 base triple and other capping structural elements that provide novel insight into structural polymorphism and heterogeneity of G-quadruplexes in general. Specific stacking interactions amongst two G-quartets flanking base triples and base pairs in TD and KDH(+) forms are reflected in 10 K higher thermal stability of KDH(+) . Populations of TD and KDH(+) forms are controlled by pH. The (de)protonation of A20 is the key for pH driven structural transformation of htel1-ΔG23. Reversibility offers possibilities for its utilization as a conformational switch within different compartments of living cell enabling specific ligand and protein interactions.

Keywords: DNA; G-quadruplexes; NMR spectroscopy; human telomere repeat; topology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA / chemistry*
  • DNA / genetics
  • G-Quadruplexes*
  • Humans
  • Hydrogen-Ion Concentration
  • Telomere / chemistry*
  • Telomere / genetics

Substances

  • DNA