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Science 314 (5807): 1903-1908

Copyright © 2006 by the American Association for the Advancement of Science

Structure of Dual Function Iron Regulatory Protein 1 Complexed with Ferritin IRE-RNA

William E. Walden,1 Anna I. Selezneva,1 Jérôme Dupuy,2 Anne Volbeda,2 Juan C. Fontecilla-Camps,2 Elizabeth C. Theil,3 Karl Volz1*

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 ~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.

1 Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612–7344, USA.
2 Laboratoire de Cristallographie et de Cristallogénèse des Protéins, IBS, Institut de Biologie Structurale Jean-Pierre Ebel; CEA; CNRS; Université Joseph Fourier, 41 rue Jules Horowitz, F-38207 Grenoble, France.
3 Children's Hospital Oakland Research Institute, Oakland, CA 94609–1673, and Department of Nutritional Science and Molecular Toxicology, University of California, Berkeley, Berkeley, CA 94720–3104, USA.

* To whom correspondence should be addressed. E-mail: kvolz{at}uic.edu


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