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

The G-rich sequence d[(G 4 CT) 3 G 4 ] 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[(G 4 CT) 3 G 4 ] displays unique features among the many G-quadruplex-forming sequences studied so far. To our knowledge d[(G 4 CT) 3 G 4 ] 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.