Slovenian NMR Center, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana, Slovenia.
Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, HR-10000, Zagreb, Croatia.
Chemistry. 2024 Jun 25;30(36):e202401190. doi: 10.1002/chem.202401190. Epub 2024 Jun 3.
We report the high-resolution NMR solution-state structure of an intramolecular G-quadruplex with a diagonal loop of ten nucleotides. The G-quadruplex is formed by a 34-nt DNA sequence, d[CAGTAGTATACTAGTAGT], named UpsB-Q-1. This sequence is found within promoters of the var genes of Plasmodium falciparum, which play a key role in malaria pathogenesis and evasion of the immune system. The [3+1]-hybrid G-quadruplex formed under physiologically relevant conditions exhibits a unique equilibrium between two structures, both stabilized by base stacking and non-canonical hydrogen bonding. Unique equilibrium of the two closely related 3D structures originates from a North-South repuckering of deoxyribose moiety of residue T27 in the lateral loop. Besides the 12 guanines involved in three G-quartets, most residues in loop regions are involved in interactions at both G-quartet-loop interfaces.
我们报告了一个具有对角线环的十核苷酸的分子内 G-四链体的高分辨率 NMR 溶液结构。该 G-四链体由 34 个核苷酸的 DNA 序列 d[CAGTAGTATACTAGTAGT]形成，命名为 UpsB-Q-1。该序列存在于恶性疟原虫 var 基因的启动子中，在疟疾发病机制和免疫系统逃避中起着关键作用。在生理相关条件下形成的 [3+1]-杂合 G-四链体表现出两种结构之间的独特平衡，这两种结构都通过碱基堆积和非经典氢键稳定。两种密切相关的 3D 结构的独特平衡源自侧环中残基 T27 的脱氧核糖部分的南北重排。除了参与三个 G-四联体的 12 个鸟嘌呤外，环区的大多数残基都参与了两个 G-四联体-环界面的相互作用。
