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PDBsum entry 1idv
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References listed in PDB file
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Key reference
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Title
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Mutational and structural analysis of stem-Loop iiic of the hepatitis c virus and gb virus b internal ribosome entry sites.
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Authors
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R.Rijnbrand,
V.Thiviyanathan,
K.Kaluarachchi,
S.M.Lemon,
D.G.Gorenstein.
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Ref.
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J Mol Biol, 2004,
343,
805-817.
[DOI no: ]
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PubMed id
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Abstract
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Translation of the open reading frames (ORF) of the hepatitis C virus (HCV) and
closely related GB virus B (GBV-B) genomes is driven by internal ribosome entry
site (IRES) elements located within the 5' non-translated RNA. The functioning
of these IRES elements is highly dependent on primary and higher order RNA
structures. We present here the solution structures of a common, critical domain
within each of these IRESs, stem-loop IIIc. These ten-nucleotide hairpins have
nearly identical sequences and similar overall tertiary folds. The final refined
structure of each shows a stem with three G:C base-pairs and a novel tetraloop
fold. Although the bases are buckled, the first and fourth nucleotides of both
tetraloops form a Watson-Crick type base-pair, while the apical nucleotides are
located in the major groove where they adopt C(2)-endo sugar puckering with
B-form geometry. No hydrogen bonding interactions were observed involving the
two apical residues of the tetraloop. Stability of the loops appears to be
derived primarily from the stacking of bases, and the hydrogen bonding between
the fourth and seventh residues. Mutational analysis shows that the primary
sequence of stem-loop IIIc is important for IRES function and that the stem and
first and fourth nucleotides of the tetraloop contribute to the efficiency of
internal ribosome entry. Base-pair formation between these two positions is
essential. In contrast, the apical loop nucleotides differ between HCV and
GBV-B, and substitutions in this region of the hairpin are tolerated without
major loss of function.
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Figure 5.
Figure 5. Final structures of stem-loop IIIc in the HCV and
GBV-B 5'NTR. Stereo view of the averaged structures for
stem-loop IIIc of HCV (A) and GBV-B (B). G residues are
indicated in blue, Cs in green, Us in purple, and As in cyan.
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Figure 6.
Figure 6. Superposition of the ten lowest energy structures
of stem-loop IIIc. Superposition of the final ten structures
with the lowest energies and NOE violations for the IIIc domains
of HCV (A) and GBV-B (B).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2004,
343,
805-817)
copyright 2004.
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Headers
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