Title
Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome
Author
Beatrice De Nicola, Christopher J. Lech, Brahim Heddi, Sagar Regmi, Ilaria Frasson, Rosalba Perrone, Sara N. Richter, Anh Tuân Phan
Year
2016
Journal
Nucleic Acids Research
Abstract
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.
Instrument
J-815
Keywords
Circular dichroism, DNA structure, Biochemistry