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PDBsum entry 2k7e
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Nucleic Acids Res
37:3342-3353
(2009)
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PubMed id:
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The structure of the human tRNALys3 anticodon bound to the HIV genome is stabilized by modified nucleosides and adjacent mismatch base pairs.
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Y.Bilbille,
F.A.Vendeix,
R.Guenther,
A.Malkiewicz,
X.Ariza,
J.Vilarrasa,
P.F.Agris.
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ABSTRACT
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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.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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N.K.Kim,
C.A.Theimer,
J.R.Mitchell,
K.Collins,
and
J.Feigon
(2010).
Effect of pseudouridylation on the structure and activity of the catalytically essential P6.1 hairpin in human telomerase RNA.
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Nucleic Acids Res,
38,
6746-6756.
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
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Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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