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Title: The structure of human tRNALys3 anticodon bound to HIV genome is stabilized by modified nucleosides and adjacent mismatch base pairs
Author: Bilbille, Yann
Vendeix, Franck A. P.
Guenther, Richard
Malkiewicz, Andrzej
Ariza Piquer, Xavier
Vilarrasa i Llorens, Jaume
Agris, Paul F.
Keywords: Sida
Genoma humà
Biologia molecular
AIDS (Disease)
Human genome
Molecular biology
Issue Date: 2009
Publisher: Oxford University Press
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.
Note: Reproducció del document publicat a:
It is part of: Nucleic Acids Research, 2009, vol. 37, num. 10, p. 3342-3353
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ISSN: 0305-1048
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

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