1r4h
From Proteopedia
(New page: 200px<br /><applet load="1r4h" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r4h" /> '''NMR Solution structure of the IIIc domain of...) |
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'''NMR Solution structure of the IIIc domain of GB Virus B IRES Element'''<br /> | '''NMR Solution structure of the IIIc domain of GB Virus B IRES Element'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Translation of the open reading frames (ORF) of the hepatitis C virus | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1R4H is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | + | 1R4H is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R4H OCA]. |
==Reference== | ==Reference== | ||
Mutational and structural analysis of stem-loop IIIC of the hepatitis C virus and GB virus B internal ribosome entry sites., Rijnbrand R, Thiviyanathan V, Kaluarachchi K, Lemon SM, Gorenstein DG, J Mol Biol. 2004 Oct 29;343(4):805-17. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15476802 15476802] | Mutational and structural analysis of stem-loop IIIC of the hepatitis C virus and GB virus B internal ribosome entry sites., Rijnbrand R, Thiviyanathan V, Kaluarachchi K, Lemon SM, Gorenstein DG, J Mol Biol. 2004 Oct 29;343(4):805-17. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15476802 15476802] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Gorenstein, D | + | [[Category: Gorenstein, D G.]] |
[[Category: Kaluarachchi, K.]] | [[Category: Kaluarachchi, K.]] | ||
| - | [[Category: Lemon, S | + | [[Category: Lemon, S M.]] |
[[Category: Rijinbrand, R.]] | [[Category: Rijinbrand, R.]] | ||
[[Category: Thiviyanathan, V.]] | [[Category: Thiviyanathan, V.]] | ||
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[[Category: ires]] | [[Category: ires]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:46:56 2008'' |
Revision as of 12:46, 21 February 2008
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NMR Solution structure of the IIIc domain of GB Virus B IRES Element
Overview
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.
About this Structure
1R4H is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Mutational and structural analysis of stem-loop IIIC of the hepatitis C virus and GB virus B internal ribosome entry sites., Rijnbrand R, Thiviyanathan V, Kaluarachchi K, Lemon SM, Gorenstein DG, J Mol Biol. 2004 Oct 29;343(4):805-17. PMID:15476802
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