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

A four-repeat human telomere DNA sequence without the 3-end guanine, d[TAGGG(TTAGGG)(2)TTAGG] (htel1-G23) 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 T18A20(+)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 10K 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-G23. Reversibility offers possibilities for its utilization as a conformational switch within different compartments of living cell enabling specific ligand and protein interactions.