Iron Regulatory Element and Internal Loop/Bulge Structure for Ferritin mRNA Studied by Cobalt(III) Hexammine Binding, Molecular Modeling, and NMR Spectroscopy

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 tran...

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Bibliographic Details
Published in:Biochemistry (Easton) Vol. 37; no. 6; pp. 1505 - 1512
Main Authors: Gdaniec, Zofia, Sierzputowska-Gracz, Hanna, Theil, Elizabeth C
Format: Journal Article
Language:English
Published: United States American Chemical Society 10-02-1998
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Summary: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 G·C base pair, conserved in ferritin IREs, spans an internal loop/bulge in the middle of an A-helix and, combined with a dynamic G·U 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.
Bibliography:ark:/67375/TPS-WX3M9WNZ-4
istex:5D1176E56886E82194628688AFE97B17A131F88B
The work was supported in part by NIH Grant DK-20251.
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ISSN:0006-2960
1520-4995
DOI:10.1021/bi9719814