Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Structure. 2010 Jan 13;18(1):73-82. doi: 10.1016/j.str.2009.10.015.
We report on the solution structure of an unprecedented intramolecular G-quadruplex formed by the guanosine-rich human chl1 intronic d(G(3)-N-G(4)-N(2)-G(4)-N-G(3)-N) 19-mer sequence in K(+)-containing solution. This G-quadruplex, composed of three stacked G-tetrads containing four syn guanines, represents a new folding topology with two unique conformational features. The first guanosine is positioned within the central G-tetrad, in contrast to all previous structures of unimolecular G-quadruplexes, where the first guanosine is part of an outermost G-tetrad. In addition, a V-shaped loop, spanning three G-tetrad planes, contains no bridging nucleotides. The G-quadruplex scaffold is stabilized by a TGA triple stacked over the G-tetrad at one end and an unpaired guanosine stacked over the G-tetrad at the other end. Finally, the chl1 intronic DNA G-quadruplex scaffold contains a guanosine base intercalated between an extended G-G step, a feature observed in common with the catalytic site of group I introns. This unique structural scaffold provides a highly specific platform for the future design of ligands specifically targeted to intronic G-quadruplex platforms.
我们报告了一个前所未有的由富含鸟嘌呤的人类 chl1 内含子 d(G(3)-N-G(4)-N(2)-G(4)-N-G(3)-N)19 -mer 序列在含 K+溶液中形成的分子内 G-四链体的溶液结构。这个 G-四链体由三个堆叠的 G-四联体组成，包含四个顺式鸟嘌呤，代表了一种具有两个独特构象特征的新折叠拓扑结构。第一个鸟嘌呤位于中央 G-四联体中，与所有以前的单分子 G-四链体结构不同，其中第一个鸟嘌呤是最外 G-四联体的一部分。此外，跨越三个 G-四联体平面的 V 形环不含桥接核苷酸。G-四链体支架由一个 TGA 三链堆积在 G-四联体的一端和一个未配对的鸟嘌呤堆积在 G-四联体的另一端稳定。最后，chl1 内含子 DNA G-四链体支架包含一个鸟嘌呤碱基插入在扩展的 G-G 步之间，这一特征与 I 组内含子的催化位点共同存在。这种独特的结构支架为未来设计专门针对内含子 G-四链体平台的配体提供了一个高度特异性的平台。
