期刊
NUCLEIC ACIDS RESEARCH
卷 44, 期 13, 页码 6442-6451出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkw432
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资金
- Singapore Ministry of Education Academic Research Fund Tier 2 [MOE2012-T2-1-102]
- Nanyang Technological University
- Bill and Melinda Gates Foundation (GCE) [OPP1035881, OPP1097238]
- European Research Council (ERC Consolidator grant) [615879]
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.
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