Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome.
The long terminal repeat (LTR) of the proviral human immunodeficiency virus (HIV)-1 genome is integral to virus transcription and host cell infection. The guanine-rich U3 region within the LTR promoter, previously shown to form G-quadruplex structures, represents an attractive target to inhibit HIV transcription and replication. In this work, we report the structure of a biologically relevant G-quadruplex within the LTR promoter region of HIV-1. The guanine-rich sequence designated LTR-IV forms a well-defined structure in physiological cationic solution. The nuclear magnetic resonance (NMR) structure of this sequence reveals a parallel-stranded G-quadruplex containing a single-nucleotide thymine bulge, which participates in a conserved stacking interaction with a neighboring single-nucleotide adenine loop. Transcription analysis in a HIV-1 replication competent cell indicates that the LTR-IV region may act as a modulator of G-quadruplex formation in the LTR promoter. Consequently, the LTR-IV G-quadruplex structure presented within this work could represent a valuable target for the design of HIV therapeutics.
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore Department of Molecular Medicine, University of Padua, Italy.
Beatrice
B
De Nicola
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
Christopher J
CJ
Lech
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
Brahim
B
Heddi
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
Sagar
S
Regmi
Department of Molecular Medicine, University of Padua, Italy.
Ilaria
I
Frasson
Department of Molecular Medicine, University of Padua, Italy.
Rosalba
R
Perrone
Department of Molecular Medicine, University of Padua, Italy sara.richter@unipd.it.
Sara N
SN
Richter
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore phantuan@ntu.edu.sg.
Anh Tuân
AT
Phan
D054856:G-Quadruplexes; D016679:Genome, Viral; D006147:Guanine / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D011533:Proviruses / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity
D006147:Guanine