Abstract
Iron regulatory protein 1 (IRP1) binds iron-responsive elements (IREs) in messenger RNAs (mRNAs), to repress translation or degradation, or binds an iron-sulfur cluster, to become a cytosolic aconitase enzyme. The 2.8 angstrom resolution crystal structure of the IRP1:ferritin H IRE complex shows an open protein conformation compared with that of cytosolic aconitase. The extended, L-shaped IRP1 molecule embraces the IRE stem-loop through interactions at two sites separated by approximately 30 angstroms, each involving about a dozen protein:RNA bonds. Extensive conformational changes related to binding the IRE or an iron-sulfur cluster explain the alternate functions of IRP1 as an mRNA regulator or enzyme.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Apoferritins / genetics*
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Binding Sites
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Crystallography, X-Ray
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Hydrogen Bonding
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Iron / metabolism
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Iron Regulatory Protein 1 / chemistry*
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Iron Regulatory Protein 1 / metabolism*
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Models, Molecular
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Nucleic Acid Conformation
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Protein Binding
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Protein Conformation
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Protein Structure, Secondary
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Protein Structure, Tertiary
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RNA, Messenger / chemistry
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Regulatory Sequences, Ribonucleic Acid*
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Response Elements*
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Sulfur / metabolism
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Untranslated Regions / chemistry*
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Untranslated Regions / metabolism*
Substances
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RNA, Messenger
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Regulatory Sequences, Ribonucleic Acid
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Untranslated Regions
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Sulfur
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Apoferritins
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Iron
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Iron Regulatory Protein 1