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2009

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cc-by-nc (c) Bilbille, Yann et al., 2009
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/41564

The structure of human tRNALys3 anticodon bound to HIV genome is stabilized by modified nucleosides and adjacent mismatch base pairs

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http://dx.doi.org/10.1093/nar/gkp187

Abstract

Replication of human immunodeficiency virus (HIV) requires base pairing of the reverse transcriptase primer, human tRNA(Lys3), to the viral RNA. Although the major complementary base pairing occurs between the HIV primer binding sequence (PBS) and the tRNA's 3'-terminus, an important discriminatory, secondary contact occurs between the viral A-rich Loop I, 5'-adjacent to the PBS, and the modified, U-rich anticodon domain of tRNA(Lys3). The importance of individual and combined anticodon modifications to the tRNA/HIV-1 Loop I RNA's interaction was determined. The thermal stabilities of variously modified tRNA anticodon region sequences bound to the Loop I of viral sub(sero)types G and B were analyzed and the structure of one duplex containing two modified nucleosides was determined using NMR spectroscopy and restrained molecular dynamics. The modifications 2-thiouridine, s(2)U(34), and pseudouridine, Psi(39), appreciably stabilized the interaction of the anticodon region with the viral subtype G and B RNAs. The structure of the duplex results in two coaxially stacked A-form RNA stems separated by two mismatched base pairs, U(162)*Psi(39) and G(163)*A(38), that maintained a reasonable A-form helix diameter. The tRNA's s(2)U(34) stabilized the interaction between the A-rich HIV Loop I sequence and the U-rich anticodon, whereas the tRNA's Psi(39) stabilized the adjacent mismatched pairs.

Subject

Sida, RNA, Genoma humà, Biologia molecular

Subject (English)

AIDS (Disease), RNA, Human genome, Molecular biology

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Articles publicats en revistes (Química Inorgànica i Orgànica)

Citation

BILBILLE, Yann, et al. The structure of human tRNALys3 anticodon bound to HIV genome is stabilized by modified nucleosides and adjacent mismatch base pairs. Nucleic Acids Research. 2009. Vol. 37, num. 10, pags. 3342-3353. ISSN 0305-1048. [consulted: 11 of August of 2026]. Available at: https://hdl.handle.net/2445/41564

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