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