Summary information and primary citation
- PDB-id
-
1fqz;
DSSR-derived features in text and
JSON formats
- Class
- RNA
- Method
- NMR
- Summary
- NMR validated model of domain iiid of hepatitis c virus
internal ribosome entry site
- Reference
-
Klinck R, Westhof E, Walker S, Afshar M, Collier A,
Aboul-Ela F (2000): "A
potential RNA drug target in the hepatitis C virus
internal ribosomal entry site." RNA,
6, 1423-1431. doi: 10.1017/S1355838200000935.
- Abstract
- 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.
