TWO CRYSTAL STRUCTURES OF D(G^ICGAGAGC) SUGGEST THAT POTASSIUM IONS MEDIATE TO FORM DNA OCTAPLEX WITH I-MOTIF OF GUANINE QUARTET

Jiro Kondo, Shun-ichi Umeda, Tomoko Sunami and Akio Takénaka

Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama 226-8501, Japan (jkondo@bio.titech.ac.jp)

DNA structures have been described in duplex forms, the two strands being aligned in the anti-parallel fashion, in general. As a special case, the telomeric DNA is assumed to form quadruplex with G-quartet and intercalated cytosine motifs (i-motif). In DNA replications, triple helix formation is required. Functional DNA would have much more complicated structures. In the present study, the two forms of crystal structures of d(G^ICGAGAGC) have been determined by X-ray analyses, to investigate the structural basis for such specific functions.

The octamer of d(G^ICGA GAGC) crystallizes in the two different forms with the space groups of I422 and I222, depending on potassium-ion con-centration. In the I422 crystal, which is obtained at relatively low potassium concentration, the octamers are assembled into an octaplex (Fig. 1a) that has never been found as the nucleic acid structure. In the central part of this novel octaplex, the G5 residues are associated around the crystallographic 4-fold axis to form the G-quartets (Fig. 2b). A potassium ion occupies the center of the octaplex for interactions with the eight O6 atoms of the G5 residues. The A4 residues also form water-mediated A-quartets (Fig. 2c) above and below the two G5-quartets. Here it is interesting to note that the octaplex is composed of the two quadruplexes, each consisting of the four parallel strands with G-quartet. The two G-quartets are intercalated into another with opposite strand polarity to form an I-motif of G-quartets (Fig. 2a).

In the I222 crystal, however, the octaplex is split away into two quadruplexes with two potassium ions (Fig. 1b), each of which contains two G-duets bound to the respective potassium. The two crystal forms suggest a dynamic transition from quadruplex to octaplex in solution. In any forms, the two adjacent anti-parallel strands form a zipper-like duplex containing two contiguous G:C pairs and a sheared G:A pair at the both ends.