Topology of a DNA G-Quadruplex Structure Formed in the HIV-1 Promoter: A Potential Target for Anti-HIV Drug Development

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• 作者：Samir Amrane ; Abdelaziz Kerkour ; Amina Bedrat ; Brune Vialet ; Marie-Line Andreola ; Jean-Louis Mergny
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：April 9, 2014
• 年：2014
• 卷：136
• 期：14
• 页码：5249-5252
• 全文大小：397K
• 年卷期：v.136,no.14(April 9, 2014)
• ISSN：1520-5126

文摘

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鈥?TGGCCTGGGCGGGACTGGG 3鈥?. This DNA fragment formed a stable two G-tetrad antiparallel G4 with an additional Watson鈥揅rick 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.