Phillips K, Dauter Z, Murchie A I, Lilley D M, Luisi B
Department of Biochemistry, Cambridge University, UK.
J Mol Biol. 1997 Oct 17;273(1):171-82. doi: 10.1006/jmbi.1997.1292.
In both DNA and RNA, stretches of guanine bases can form stable four-stranded helices in the presence of sodium or potassium ions. Sequences with a propensity to form guanine tetraplexes have been found in chromosomal telomers, immunoglobulin switch regions, and recombination sites. We report the crystal structure at 0.95 A resolution of a parallel-stranded tetraplex formed by the hexanucleotide d(TG4T) in the presence of sodium ions. The four strands form a right-handed helix that is stabilized by hydrogen-bonding tetrads of co-planar guanine bases. Well-resolved sodium ions are found between and, at defined points, within tetrad planes and are coordinated with the guanine O6 groups. Nine calcium ions have been identified, each with a well-defined hepta-coordinate hydration shell. Hydrogen-bonding water patterns are observed within the tetraplex's helical grooves and clustered about the phosphate groups. Water molecules in the groove may form a hydrogen bond 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 that the sugar conformation is strained and propose that this originates from forces that optimize guanine base stacking. Discrete conformational disorder is observed at several places in the phosphodiester backbone, which results from a simple crankshaft rotation that requires no net change in the sugar conformation.
在DNA和RNA中，鸟嘌呤碱基片段在存在钠离子或钾离子的情况下可形成稳定的四链螺旋结构。在染色体端粒、免疫球蛋白转换区和重组位点中已发现有形成鸟嘌呤四链体倾向的序列。我们报道了六核苷酸d(TG4T)在钠离子存在下形成的平行链四链体的0.95埃分辨率晶体结构。四条链形成一个右手螺旋，由共面鸟嘌呤碱基的氢键四重体稳定。在四重体平面之间以及特定位置发现了分辨率良好的钠离子，它们与鸟嘌呤的O6基团配位。已鉴定出九个钙离子，每个钙离子都有一个定义明确的七配位水合壳。在四链体的螺旋凹槽内观察到氢键水模式，并围绕磷酸基团聚集。凹槽中的水分子可能与O4'形成氢键，并可能影响鸟嘌呤的堆积行为。鸟嘌呤四重体有两种不同的堆积排列方式。胸腺嘧啶碱基不参与四链构象，而是堆积以稳定晶格。我们提供证据表明糖构象受到应变，并提出这源于优化鸟嘌呤碱基堆积的力。在磷酸二酯主链的几个位置观察到离散的构象无序，这是由简单的曲轴旋转导致的，在糖构象中不需要净变化。
