Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome
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...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2018
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| Online Access: | https://hdl.handle.net/10356/88976 http://hdl.handle.net/10220/46042 |
| _version_ | 1826115394392293376 |
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| author | De Nicola, Beatrice Lech, Christopher J. Heddi, Brahim Regmi, Sagar Frasson, Ilaria Perrone, Rosalba Richter, Sara N. Phan, Anh Tuân |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences De Nicola, Beatrice Lech, Christopher J. Heddi, Brahim Regmi, Sagar Frasson, Ilaria Perrone, Rosalba Richter, Sara N. Phan, Anh Tuân |
| author_sort | De Nicola, Beatrice |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T03:54:44Z |
| format | Journal Article |
| id | ntu-10356/88976 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:54:44Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/889762023-02-28T19:32:56Z Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome De Nicola, Beatrice Lech, Christopher J. Heddi, Brahim Regmi, Sagar Frasson, Ilaria Perrone, Rosalba Richter, Sara N. Phan, Anh Tuân School of Physical and Mathematical Sciences Nuclear Magnetic Resonance (NMR) DRNTU::Science::Physics Long Terminal Repeat (LTR) 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. MOE (Min. of Education, S’pore) 2018-09-19T08:41:04Z 2019-12-06T17:15:03Z 2018-09-19T08:41:04Z 2019-12-06T17:15:03Z 2016 Journal Article De Nicola, B., Lech, C. J., Heddi, B., Regmi, S., Frasson, I., Perrone, R., . . . Phan, A. T. (2016). Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome. Nucleic Acids Research, 44(13), 6442-6451. doi:10.1093/nar/gkw432 0305-1048 https://hdl.handle.net/10356/88976 http://hdl.handle.net/10220/46042 10.1093/nar/gkw432 en Nucleic Acids Research © 2016 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. 10 p. application/pdf |
| spellingShingle | Nuclear Magnetic Resonance (NMR) DRNTU::Science::Physics Long Terminal Repeat (LTR) De Nicola, Beatrice Lech, Christopher J. Heddi, Brahim Regmi, Sagar Frasson, Ilaria Perrone, Rosalba Richter, Sara N. Phan, Anh Tuân Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome |
| title | Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome |
| title_full | Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome |
| title_fullStr | Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome |
| title_full_unstemmed | Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome |
| title_short | Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome |
| title_sort | structure and possible function of a g quadruplex in the long terminal repeat of the proviral hiv 1 genome |
| topic | Nuclear Magnetic Resonance (NMR) DRNTU::Science::Physics Long Terminal Repeat (LTR) |
| url | https://hdl.handle.net/10356/88976 http://hdl.handle.net/10220/46042 |
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