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ETUDE CRISTALLOGRAPHIQUE DE LA PROTEINE IRP1 (IRON REGULATORY PROTEIN 1), UN REGULATEUR DE L'HOMEOSTASIE DU FER.

Abstract : In animals, two highly homologous cytosolic Iron Regulatory Proteins, IRP1 and IRP2, are involved in the metabolism of this biologically essential metal. Both proteins can bind to specific mRNA regions called Iron Responsive Elements and thereby control the expression of proteins involved in the uptake, storage and utilization of iron. IRP1 loses its RNA-binding ability in its major form found in most tissues and normal cell cultures, wherein it contains a [4Fe-4S] cluster and becomes a cytosolic aconitase, catalyzing the conversion of citrate to isocitrate. The exact physiological role of IRP1 is still not entirely clear, but there are indications that it may be involved in oxidative stress response.
Human IRP1 has a molecular mass of 98 kDa. We have been able to crystallize this [4Fe-4S]-containing form under anaerobic conditions and collected X-ray diffraction data up to a maximum resolution of 1.85 Å. Attempts to solve the structure by molecular replacement, using the structure of the homologous bovine mitochondrial aconitase which shows about 22% sequence identity with IRP1, did not work. Subsequently, a second slightly different crystal form diffracting to 2.5 Å resolution was obtained. Anomalous signals of the iron-sulfur cluster and a fortuitous zinc site in the native enzyme and data from an isomorphous gold derivative of this crystal form have been successfully used for phasing. The structure have been refined and analyzed with respect to its aconitase and potential RNA-binding functions, using the results from numerous site-directed mutagenesis and other studies that are available in the literature.
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https://tel.archives-ouvertes.fr/tel-00411037
Contributor : Jerome Dupuy <>
Submitted on : Tuesday, August 25, 2009 - 4:22:35 PM
Last modification on : Wednesday, October 14, 2020 - 4:17:44 AM
Long-term archiving on: : Tuesday, June 15, 2010 - 9:03:23 PM

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  • HAL Id : tel-00411037, version 1

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Jérôme Dupuy. ETUDE CRISTALLOGRAPHIQUE DE LA PROTEINE IRP1 (IRON REGULATORY PROTEIN 1), UN REGULATEUR DE L'HOMEOSTASIE DU FER.. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2005. Français. ⟨tel-00411037⟩

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