1fqz
From Proteopedia
(New page: 200px<br /><applet load="1fqz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fqz" /> '''NMR VALIDATED MODEL OF DOMAIN IIID OF HEPATI...) |
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| - | [[Image:1fqz.gif|left|200px]]<br /><applet load="1fqz" size=" | + | [[Image:1fqz.gif|left|200px]]<br /><applet load="1fqz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1fqz" /> | caption="1fqz" /> | ||
'''NMR VALIDATED MODEL OF DOMAIN IIID OF HEPATITIS C VIRUS INTERNAL RIBOSOME ENTRY SITE'''<br /> | '''NMR VALIDATED MODEL OF DOMAIN IIID OF HEPATITIS C VIRUS INTERNAL RIBOSOME ENTRY SITE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Subdomain IlId from the hepatitis C virus (HCV) internal ribosome entry | + | Subdomain IlId from the hepatitis C virus (HCV) internal ribosome entry site (IRES) has been shown to be essential for cap-independent translation. We have conducted a structural study of a 27-nt fragment, identical in sequence to IlId, to explore the structural features of this subdomain. The proposed secondary structure of IlId is comprised of two 3 bp helical regions separated by an internal loop and closed at one end by a 6-nt terminal loop. NMR and molecular modeling were used interactively to formulate a validated model of the three-dimensional structure of IlId. We found that this fragment contains several noncanonical structural motifs and non-Watson-Crick base pairs, some of which are common to other RNAs. In particular, a motif characteristic of the rRNA alpha-sarcin/ricin loop was located in the internal loop. The terminal loop, 5'-UUGGGU, was found to fold to form a trinucleotide loop closed by a trans-wobble U.G base pair. The sixth nucleotide was bulged out to allow stacking of this U.G pair on the adjacent helical region. In vivo mutational analysis in the context of the full IRES confirmed the importance of each structural motif within IIId for IRES function. These findings may provide clues as to host cellular proteins that play a role in IRES-directed translation and, in particular, the mechanism through which host ribosomes are sequestered for viral function. |
==About this Structure== | ==About this Structure== | ||
| - | 1FQZ 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:// | + | 1FQZ 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=1FQZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Westhof, E.]] | [[Category: Westhof, E.]] | ||
[[Category: loop e motif]] | [[Category: loop e motif]] | ||
| - | [[Category: reverse hoogsteen a | + | [[Category: reverse hoogsteen a u pair]] |
[[Category: s-turn]] | [[Category: s-turn]] | ||
[[Category: sarcin-ricin loop]] | [[Category: sarcin-ricin loop]] | ||
| - | [[Category: sheared g | + | [[Category: sheared g a pair]] |
| - | [[Category: trans wobble g | + | [[Category: trans wobble g u pair]] |
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:41:41 2008'' |
Revision as of 10:41, 21 February 2008
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NMR VALIDATED MODEL OF DOMAIN IIID OF HEPATITIS C VIRUS INTERNAL RIBOSOME ENTRY SITE
Overview
Subdomain IlId from the hepatitis C virus (HCV) internal ribosome entry site (IRES) has been shown to be essential for cap-independent translation. We have conducted a structural study of a 27-nt fragment, identical in sequence to IlId, to explore the structural features of this subdomain. The proposed secondary structure of IlId is comprised of two 3 bp helical regions separated by an internal loop and closed at one end by a 6-nt terminal loop. NMR and molecular modeling were used interactively to formulate a validated model of the three-dimensional structure of IlId. We found that this fragment contains several noncanonical structural motifs and non-Watson-Crick base pairs, some of which are common to other RNAs. In particular, a motif characteristic of the rRNA alpha-sarcin/ricin loop was located in the internal loop. The terminal loop, 5'-UUGGGU, was found to fold to form a trinucleotide loop closed by a trans-wobble U.G base pair. The sixth nucleotide was bulged out to allow stacking of this U.G pair on the adjacent helical region. In vivo mutational analysis in the context of the full IRES confirmed the importance of each structural motif within IIId for IRES function. These findings may provide clues as to host cellular proteins that play a role in IRES-directed translation and, in particular, the mechanism through which host ribosomes are sequestered for viral function.
About this Structure
1FQZ is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
A potential RNA drug target in the hepatitis C virus internal ribosomal entry site., Klinck R, Westhof E, Walker S, Afshar M, Collier A, Aboul-Ela F, RNA. 2000 Oct;6(10):1423-31. PMID:11073218
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