A bacterial DNA quadruplex with exceptional K+ selectivity and unique structural polymorphism

Abstract

The G-rich sequence d[(G₄CT)₃G₄] was recently identified as a potential quadruplex-forming sequence associated with loci involved in antigenic variation in the human pathogen Treponema pallidum. We found this motif to be enriched in eubacterial genomes. Employing a combination of CD spectroscopy, EPR spectroscopy, analytical ultracentrifugation, and EMSA, we demonstrate that d[(G₄CT)₃G₄] displays unique features among the many G-quadruplex-forming sequences studied so far. To our knowledge d[(G₄CT)₃G₄] shows a so far unprecedented selectivity for K⁺ with even high concentrations of Na⁺ unable to induce pronounced G-quadruplex formation. A remarkable continuous and complete transition from an anti-parallel, monomolecular structure into a tetrameric, parallel conformation is observed upon increasing K⁺-concentrations. Furthermore we investigate the effects of cation selectivity, quadruplex loop composition and length as well as G-tract length on quadruplex conversion.