Structure of the human telomere in Na+ solution : an antiparallel (2+2) G-quadruplex scaffold reveals additional diversity

Abstract

Single-stranded DNA overhangs at the ends of human telomeric repeats are capable of adopting four-stranded G-quadruplex structures, which could serve as potential anticancer targets. Out of the five reported intramolecular human telomeric G-quadruplex structures, four were formed in the presence of K+ ions and only one in the presence of Na+ ions, leading often to a perception that this structural polymorphism occurs exclusively in the presence of K+ but not Na+. Here we present the structure of a new antiparallel (2+2) G-quadruplex formed by a derivative of a 27-nt human telomeric sequence in Na+ solution, which comprises a novel core arrangement distinct from the known topologies. This structure complements the previously elucidated basket-type human telomeric G-quadruplex to serve as reference structures in Na+-containing environment. These structures, together with the coexistence of other conformations in Na+ solution as observed by nuclear magnetic resonance spectroscopy, establish the polymorphic nature of human telomeric repeats beyond the influence of K+ ions.