Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/139296
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.
URI: https://hdl.handle.net/10356/139296
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

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