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

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

De Nicola B,Lech CJ,Heddi B,Regmi S,Frasson I,Perrone R,Richter SN,Phan AT

doi

10.1093/nar/gkw432

subject

Has Abstract

pub_date

2016-07-27 00:00:00

pages

6442-51

issue

13

eissn

0305-1048

issn

1362-4962

pii

gkw432

journal_volume

44

pub_type

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