THE CRYSTAL-STRUCTURE OF A PARALLEL-STRANDED GUANINE TETRAPLEX AT 0.95 ANGSTROM RESOLUTION

Ln both DNA and RNA, stretches of guanine bases can form stable four-s tranded helices in the presence of sodium or potassium ions. Sequences with a propensity to form guanine tetraplexes have been found in chro mosomal telomers, immunoglobulin switch regions, and recombination sit es. We report the crystal structure at 0.95 Angstrom resolution of a p arallel-stranded tetraplex formed by the hexanucleotide d(TG(4)T) in t he presence of sodium ions. The four strands form a right-handed helix that is stabilized by hydrogen-bonding tetrads of co-planar guanine b ases. Well-resolved sodium ions are found between and, at defined poin ts, within tetrad planes and are coordinated with the guanine O6 group s. Nine calcium ions have been identified, each with a well-defined he pta-coordinate hydration shell. Hydrogen-bonding water patterns are ob served within the tetraplex's helical grooves and clustered about the phosphate groups. Water molecules in the groove may form a hydrogen bo nd with the O4', and may affect the stacking behavior of guanine. Two distinct stacking arrangements are noted for the guanine tetrads. The thymine bases do not contribute to the four-stranded conformation, but instead stack to stabilize the crystal lattice. We present evidence t hat the sugar conformation is strained and propose that this originate s from forces that optimize guanine base stacking. Discrete conformati onal disorder is observed at several places in the phosphodiester back bone, which results from a simple crankshaft rotation that requires no net change in the sugar conformation. (C) 1997 Academic Press Limited .