DMCA
Iron regulatory element and internal loop/bulge structure for ferritin mRNA studied by cobalt(III) hexamine binding, molecular modeling and NMR spectroscopy (1998)
| Venue: | Biochemistry |
| Citations: | 13 - 1 self |
BibTeX
@ARTICLE{Gdaniec98ironregulatory,
author = {Zofia Gdaniec and Hanna Sierzputowska-gracz and Elizabeth C. Theil},
title = {Iron regulatory element and internal loop/bulge structure for ferritin mRNA studied by cobalt(III) hexamine binding, molecular modeling and NMR spectroscopy},
journal = {Biochemistry},
year = {1998},
pages = {1505--1512}
}
Share
 |
 |
 |
 |
||
OpenURL
Abstract
ABSTRACT: The ferritin IRE, a highly conserved (96-99 % in vertebrates) mRNA translation regulatory element in animal mRNA, was studied by molecular modeling (using MC-SYM and DOCKING) and by NMR spectroscopy. Cobalt(III) hexammine was used to model hydrated Mg2+. IRE isoforms in other mRNAs regulate mRNA translation or stability; all IREs bind IRPs (iron regulatory proteins). A GâC base pair, conserved in ferritin IREs, spans an internal loop/bulge in the middle of an A-helix and, combined with a dynamic GâU base pair, formed a pocket suitable for Co(III) hexammine binding. On the basis of the effects of Co(III) hexammine on the 1H NMR spectrum and results of automatic docking into the IRE model, the IRE bound Co(III) hexammine at the pocket in the major groove; Mg2+ may bind to the IRE at the same site on the basis of an analogy to Co(III) hexammine and on the Mg2+ inhibition of Cu-(phen)2 cleavage at the site. Distortion of the IRE helix by the internal loop/bulge near a conserved unpaired C required for IRP binding and adjacent to an IRP cross-linking site suggests a role for the pocket in ferritin IRE/IRP interactions. RNA sequences in the noncoding region of mRNAs can regulate mRNA function. The predicted secondary structure is a hairpin distorted by a bulge, bulge loop, or internal loop.
Keyphrases
molecular modeling nmr spectroscopy iron regulatory element internal loop bulge structure ferritin mrna hexamine binding ferritin ire internal loop bulge animal mrna dynamic base pair translation regulatory element ferritin ire irp interaction irp binding ire bound co mrna function bulge loop irp cross-linking site iron regulatory protein ire helix mrna regulate mrna translation predicted secondary structure internal loop nmr spectrum major groove hydrated mg2 ire isoforms rna sequence automatic docking base pair ire model noncoding region mg2 inhibition
