Light rare earth elements stabilize G-quadruplex structure in variants of human telomeric sequences

Recently, light rare earth elements (LREEs) are gaining importance in modern-day technologies. Thus, the entry of LREEs into biochemical pathways cannot be ignored, which might affect the conformation of biomacromolecules. Herein, for the first time, we discover the G-quadruplex formation in the human telomeric variants in presence of micromolar concentrations of LREEs. Thermal melting show that the LREE-induced unimolecular G-quadruplex structure. Isothermal titration calorimetry, UV-vis, and CD spectroscopy results suggest the binding stoichiometry of lanthanide ions to telomeric variants is 2:1. The data confirms that the LREE ions coordinate between adjacent G-quartets. The excess LREE ions are most likely binding to quadruplex loops. The CD spectra revealed that the LREE-induced quadruplex in human telomere and its variant have antiparallel orientation. The binding equilibria of LREEs have been studied both in the presence and absence of competing metal cations. Addition of LREEs to the Na⁺ or K⁺-induced G-quadruplexes led to conformational change, which may be ascribed to the displacement of K⁺ or Na⁺ ions by LREE ions and formation of a more compact LREE-induced G-quadruplex structure in human telomeric variant. Moreover, the thymine in the central loop of the human telomeric sequence stabilizes LREE induced G-quadruplex.