Basilion J P, Rouault T A, Massinople C M, Klausner R D, Burgess W H
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):574-8. doi: 10.1073/pnas.91.2.574.
The iron-responsive element-binding protein (IRE-BP) binds to specific stem-loop RNA structures known as iron-responsive elements (IREs) present in a variety of cellular mRNAs (e.g., those encoding ferritin, erythroid 5-aminolevulinate synthase, and transferrin receptor). Expression of these genes is regulated by interaction with the IRE-BP. The IRE-BP is identical in sequence to cytosolic aconitase, and the function of the protein is determined by the presence or absence of an Fe-S cluster. The protein either functions as an active aconitase when the Fe-S cluster is present or as an RNA-binding protein when the protein lacks this cluster. Aconitase activity and IRE-binding activity are mutually exclusive, and interconversion between the two activities is determined by intracellular Fe concentrations. Mapping of the RNA-binding site of the IRE-BP by UV cross-linking studies defines a major contact site between IRE and protein in the active-site region. Modeling based on probable structural similarities between the previously crystallized mitochondrial aconitase and the IRE-BP predicts that these residues would be accessible to the IRE only were there a major change in the predicted conformation of the protein when cells are iron-depleted.
铁反应元件结合蛋白（IRE-BP）与特定的茎环RNA结构结合，这些结构被称为铁反应元件（IREs），存在于多种细胞mRNA中（例如，那些编码铁蛋白、红细胞5-氨基酮戊酸合酶和转铁蛋白受体的mRNA）。这些基因的表达通过与IRE-BP的相互作用来调节。IRE-BP在序列上与胞质乌头酸酶相同，该蛋白的功能由铁硫簇的存在与否决定。当存在铁硫簇时，该蛋白作为活性乌头酸酶发挥作用；当缺乏该簇时，则作为RNA结合蛋白发挥作用。乌头酸酶活性和IRE结合活性相互排斥，两种活性之间的相互转换由细胞内铁浓度决定。通过紫外线交联研究对IRE-BP的RNA结合位点进行定位，确定了IRE与活性位点区域中蛋白质之间的主要接触位点。基于先前结晶的线粒体乌头酸酶和IRE-BP之间可能的结构相似性进行的建模预测，只有当细胞缺铁时蛋白质的预测构象发生重大变化，这些残基才会对IRE可及。
