Crystal structure of a DNA/Ba2+ G-quadruplex containing a water-mediated C-tetrad

We have determined the 1.50 angstrom A crystal structure of the DNA decamer, d(CCA(CNV)KGCGTGG) (K-CNV, 3-cyanovinylcarbazole), which forms a G-quadruplex structure in the presence of Ba2+. The structure contains several unique features including a bulged nucleotide and the first crystal structure observation of a C-tetrad. The structure reveals that water molecules mediate contacts between the divalent cations and the C-tetrad, allowing Ba2+ ions to occupy adjacent steps in the central ion channel. One ordered Mg2+ facilitates 3'-3' stacking of two quadruplexes in the asymmetric unit, while the bulged nucleotide mediates crystal contacts. Despite the high diffraction limit, the first four nucleotides including the K-CNV nucleoside are disordered though they are still involved in crystal packing. This work suggests that the bulky hydrophobic groups may locally influence the formation of non-Watson-Crick structures from otherwise complementary sequences. These observations lead to the intriguing possibility that certain types of DNA damage may act as modulators of G-quadruplex formation.