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Crystal structure of human iron regulatory protein 1 as cytosolic aconitase.

Dupuy J, Volbeda A, Carpentier P, Darnault C, Moulis JM, Fontecilla-Camps JC
Structure 14 129-39 (2006)
Cited: 100 times
EuropePMC logo PMID: 16407072

Abstract

Iron regulatory proteins (IRPs) control the translation of proteins involved in iron uptake, storage and utilization by binding to specific noncoding sequences of the corresponding mRNAs known as iron-responsive elements (IREs). This strong interaction assures proper iron homeostasis in animal cells under iron shortage. Conversely, under iron-replete conditions, IRP1 binds a [4Fe-4S] cluster and functions as cytosolic aconitase. Regulation of the balance between the two IRP1 activities is complex, and it does not depend only on iron availability. Here, we report the crystal structure of human IRP1 in its aconitase form. Comparison with known structures of homologous enzymes reveals well-conserved folds and active site environments with significantly different surface shapes and charge distributions. The specific features of human IRP1 allow us to propose a tentative model of an IRP1-IRE complex that agrees with a range of previously obtained data.

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Related citations provided by authors (1)

  1. Crystallization and Preliminary X-Ray Diffraction Data For the Aconitase Form of Human Iron Regulatory Protein 1. Dupuy J, DARNAULT C, BRAZZOLOTTO X, KUHN LC, MOULIS JM, Volbeda A, Fontecilla-Camps JC Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 61 482-485 (2005)

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