Please use this identifier to cite or link to this item:
Title: Major G‑quadruplex form of HIV‑1 LTR reveals a (3+1) folding topology containing a stem-loop
Authors: Butovskaya, Elena
Heddi, Brahim
Bakalar, Blaž
Richter, Sara N.
Phan, Anh Tuân
Keywords: Science::Biological sciences
Issue Date: 2018
Source: Butovskaya, E., Heddi, B., Bakalar, B., Richter, S. N., & Phan, A. T. (2018). Major G-quadruplex form of HIV-1 LTR reveals a (3+1) folding topology containing a stem-loop. Journal of the American Chemical Society, 140(42), 13654-13662. doi:10.1021/jacs.8b05332
Journal: Journal of the American Chemical Society
Abstract: Nucleic acids can form noncanonical four-stranded structures called G-quadruplexes. G-quadruplex-forming sequences are found in several genomes including human and viruses. Previous studies showed that the G-rich sequence located in the U3 promoter region of the HIV-1 long terminal repeat (LTR) folds into a set of dynamically interchangeable G-quadruplex structures. G-quadruplexes formed in the LTR could act as silencer elements to regulate viral transcription. Stabilization of LTR G-quadruplexes by G-quadruplex-specific ligands resulted in decreased viral production, suggesting the possibility of targeting viral G-quadruplex structures for antiviral purposes. Among all the G-quadruplexes formed in the LTR sequence, LTR-III was shown to be the major G-quadruplex conformation in vitro. Here we report the NMR structure of LTR-III in K+ solution, revealing the formation of a unique quadruplex-duplex hybrid consisting of a three-layer (3 + 1) G-quadruplex scaffold, a 12-nt diagonal loop containing a conserved duplex-stem, a 3-nt lateral loop, a 1-nt propeller loop, and a V-shaped loop. Our structure showed several distinct features including a quadruplex-duplex junction, representing an attractive motif for drug targeting. The structure solved in this study may be used as a promising target to selectively impair the viral cycle.
ISSN: 0002-7863
DOI: 10.1021/jacs.8b05332
Rights: © 2018 American Chemical Society. This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SPMS Journal Articles

Citations 50

Updated on Jan 15, 2021

Citations 50

Updated on Jan 21, 2021

Page view(s) 50

Updated on Jan 22, 2021


Updated on Jan 22, 2021

Google ScholarTM




Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.