Summary information and primary citation
- PDB-id
-
2gvo;
DSSR-derived features in text and
JSON formats
- Class
- RNA
- Method
- NMR
- Summary
- Solution structure of a purine rich hexaloop hairpin
belonging to pgy-mdr1 mrna and targeted by antisense
oligonucleotides
- Reference
-
Joli F, Bouchemal N, Laigle A, Hartmann B, Hantz E
(2006): "Solution
structure of a purine rich hexaloop hairpin belonging to
PGY/MDR1 mRNA and targeted by antisense
oligonucleotides." Nucleic Acids Res.,
34, 5740-5751. doi: 10.1093/nar/gkl617.
- Abstract
- A preferential target of antisense oligonucleotides
directed against human PGY/MDR1 mRNA is a hairpin
containing a stem with a G*U wobble pair, capped by the
purine-rich 5'r(GGGAUG)3' hexaloop. This hairpin is studied
by multidimensional NMR and restrained molecular dynamics,
with special emphasis on the conformation of south sugars
and non-standard phosphate linkages evidenced in both the
stem and the loop. The hairpin is found to be highly
structured. The G*U wobble pair, a strong counterion
binding site, displays structural particularities that are
characteristic of this type of mismatch. The upper part of
the stem undergoes distortions that optimize its
interactions with the beginning of the loop. The loop
adopts a new fold in which the single-stranded GGGA purine
tract is structured in A-like conformation stacked in
continuity of the stem and displays an extensive hydrogen
bonding surface for recognition. The remarkable hairpin
stability results from classical inter- and intra-strand
interactions reinforced by numerous hydrogen bonds
involving unusual backbone conformations and ribose
2'-hydroxyl groups. Overall, this work emphasizes numerous
features that account for the well-ordered structure of the
whole hairpin and highlights the loop properties that
facilitate interaction with antisense
oligonucleotides.
