title: Topology of a DNA G-quadruplex structure formed in the HIV-1 promoter: a potential target for anti-HIV drug development.
abstract: 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.
authors.affiliation: Université de Bordeaux , 33000 Bordeaux, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Amrane
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Kerkour
authors.forename: Amina
authors.initials: A
authors.lastname: Bedrat
authors.forename: Brune
authors.initials: B
authors.lastname: Vialet
authors.forename: Marie-Line
authors.initials: ML
authors.lastname: Andreola
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mergny
mesh_terms: D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004279:DNA, Viral / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D054856:G-Quadruplexes / Q000187:drug effects*; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics*; D008024:Ligands; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D000166:Acridines; D019380:Anti-HIV Agents; D004279:DNA, Viral; D008024:Ligands; C454064:BRACO-19