PDBsum entry 1idv

RNA

PDB id: 1idv

Contents

DNA/RNA

PDB id:

1idv

Name:

RNA

Title:

Nmr structure of hcv ires RNA domain iiic

Structure:

Hepatitis c ires RNA domain iiic. Chain: a. Engineered: yes

Source:

Synthetic: yes. Other_details: synthesized by in vitro transcription using t7 RNA polymerase

NMR struc:

10 models

Authors:

K.Kaluarachchi,R.Rijnbrand,S.M.Lemon,D.G.Gorenstein

Key ref:

R.Rijnbrand et al. (2004). Mutational and structural analysis of stem-loop IIIC of the hepatitis C virus and GB virus B internal ribosome entry sites. J Mol Biol, 343, 805-817. PubMed id: 15476802 DOI: 10.1016/j.jmb.2004.08.095

Date:

05-Apr-01 Release date: 05-Oct-01

DNA/RNA chain

G-G-G-C-G-U-G-C-C-C 10 bases

DOI no: 10.1016/j.jmb.2004.08.095

J Mol Biol 343:805-817 (2004)

PubMed id: 15476802

Mutational and structural analysis of stem-loop IIIC of the hepatitis C virus and GB virus B internal ribosome entry sites.

R.Rijnbrand, V.Thiviyanathan, K.Kaluarachchi, S.M.Lemon, D.G.Gorenstein.

ABSTRACT

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.

Selected figure(s)

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.

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).

The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 343, 805-817) copyright 2004.

Figures were selected by an automated process.