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Nucleic Acids Res. 2016 Jul 27;44(13):6442-51. doi: 10.1093/nar/gkw432. Epub 2016 Jun 13.

Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome.

Author information

1
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore Department of Molecular Medicine, University of Padua, Italy.
2
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
3
Department of Molecular Medicine, University of Padua, Italy.
4
Department of Molecular Medicine, University of Padua, Italy sara.richter@unipd.it.
5
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore phantuan@ntu.edu.sg.

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.

PMID:
27298260
PMCID:
PMC5291261
DOI:
10.1093/nar/gkw432
[Indexed for MEDLINE]
Free PMC Article

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