Université de Bordeaux , 33000 Bordeaux, France.
J Am Chem Soc. 2014 Apr 9;136(14):5249-52. doi: 10.1021/ja501500c. Epub 2014 Mar 27.
Nucleic acid sequences containing guanine tracts are able to adopt noncanonical four-stranded nucleic acid structures called G-quadruplexes (G4s). These structures are based on the stacking of two or more G-tetrads; each tetrad is a planar association of four guanines held together by eight hydrogen bonds. In this study, we analyzed a conserved G-rich region from HIV-1 promoter that is known to regulate the transcription of the HIV-1 provirus. Strikingly, our analysis of an alignment of 1684 HIV-1 sequences from this region showed a high conservation of the ability to form G4 structures despite a lower conservation of the nucleotide primary sequence. Using NMR spectroscopy, we determined the G4 topology adopted by a DNA sequence from this region (HIV-PRO1: 5' TGGCCTGGGCGGGACTGGG 3'). This DNA fragment formed a stable two G-tetrad antiparallel G4 with an additional Watson-Crick CG base pair. This hybrid structure may be critical for HIV-1 gene expression and is potentially a novel target for anti-HIV-1 drug development.
含有鸟嘌呤链的核酸序列能够采用非典型的四链核酸结构，称为 G-四联体 (G4s)。这些结构基于两个或更多 G-四联体的堆叠；每个四联体是由八个氢键保持在一起的四个鸟嘌呤的平面缔合。在这项研究中，我们分析了 HIV-1 启动子中一个保守的富含鸟嘌呤的区域，该区域已知可调节 HIV-1 前病毒的转录。引人注目的是，尽管核苷酸一级序列的保守性较低，但我们对来自该区域的 1684 个 HIV-1 序列的比对分析表明，形成 G4 结构的能力具有高度保守性。我们使用 NMR 光谱学确定了来自该区域的一个 DNA 序列（HIV-PRO1：5' TGGCCTGGGCGGGACTGGG 3'）采用的 G4 拓扑结构。该 DNA 片段形成了一个稳定的具有额外 Watson-Crick CG 碱基对的两个 G-四联体反平行 G4。这种混合结构可能对 HIV-1 基因表达至关重要，并且可能是抗 HIV-1 药物开发的新靶标。
