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

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• 作者：Zofia Gdaniec ; Hanna Sierzputowska-Gracz ; and Elizabeth C. Theil
• 刊名：Biochemistry
• 出版年：1998
• 出版时间：February 10, 1998
• 年：1998
• 卷：37
• 期：6
• 页码：1505 - 1512
• 全文大小：182K
• 年卷期：v.37,no.6(February 10, 1998)
• ISSN：1520-4995

文摘

The ferritin IRE, a highly conserved (96-99% in vertebrates)mRNA translation regulatoryelement in animal mRNA, was studied by molecular modeling (using MC-SYMand DOCKING) and byNMR spectroscopy. Cobalt(III) hexammine was used to modelhydrated Mg²⁺. IRE isoforms in othermRNAs regulate mRNA translation or stability; all IREs bind IRPs (ironregulatory proteins). A G·Cbase pair, conserved in ferritin IREs, spans an internal loop/bulge inthe middle of an A-helix and, combinedwith a dynamic G·U base pair, formed a pocket suitable forCo(III) hexammine binding. On the basis ofthe effects of Co(III) hexammine on the ¹H NMRspectrum and results of automatic docking into the IREmodel, the IRE bound Co(III) hexammine at the pocket in the majorgroove; Mg²⁺ may bind to the IREat the same site on the basis of an analogy to Co(III) hexammineand on the Mg²⁺ inhibition of Cu(phen)₂ cleavage at the site. Distortion of the IREhelix by the internal loop/bulge near a conservedunpaired C required for IRP binding and adjacent to an IRPcross-linking site suggests a role for thepocket in ferritin IRE/IRP interactions.