Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Structure of Dual Function Iron Regulatory Protein 1 Complexed with Ferritin IRE-RNA
William E. Walden,1Anna I. Selezneva,1Jérôme Dupuy,2Anne Volbeda,2Juan C. Fontecilla-Camps,2Elizabeth C. Theil,3Karl Volz1*
Iron regulatory protein 1 (IRP1) binds iron-responsive elements(IREs) in messenger RNAs (mRNAs), to repress translation ordegradation, or binds an iron-sulfur cluster, to become a cytosolicaconitase enzyme. The 2.8 angstrom resolution crystal structureof the IRP1:ferritin H IRE complex shows an open protein conformationcompared with that of cytosolic aconitase. The extended, L-shapedIRP1 molecule embraces the IRE stem-loop through interactionsat two sites separated by 30 angstroms, each involving abouta dozen protein:RNA bonds. Extensive conformational changesrelated to binding the IRE or an iron-sulfur cluster explainthe 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
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Tracey A. Rouault (22 December 2006) Science314 (5807), 1886.
[DOI: 10.1126/science.1137174] |Summary »|Full Text »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Tempol-mediated activation of latent iron regulatory protein activity prevents symptoms of neurodegenerative disease in IRP2 knockout mice.
M. C. Ghosh, W.-H. Tong, D. Zhang, H. Ollivierre-Wilson, A. Singh, M. C. Krishna, J. B. Mitchell, and T. A. Rouault (2008)
PNAS
105, 12028-12033
|Abstract »|Full Text »|PDF »
DNA mimicry by a high-affinity anti-NF-{kappa}B RNA aptamer.
N. J. Reiter, L. J. Maher III, and S. E. Butcher (2008)
Nucleic Acids Res.
36, 1227-1236
|Abstract »|Full Text »|PDF »
Zinc Deficiency-induced Iron Accumulation, a Consequence of Alterations in Iron Regulatory Protein-binding Activity, Iron Transporters, and Iron Storage Proteins.
B. J. Niles, M. S. Clegg, L. A. Hanna, S. S. Chou, T. Y. Momma, H. Hong, and C. L. Keen (2008)
J. Biol. Chem.
283, 5168-5177
|Abstract »|Full Text »|PDF »
Ferritin L and H Subunits Are Differentially Regulated on a Post-transcriptional Level.
M. C. Sammarco, S. Ditch, A. Banerjee, and E. Grabczyk (2008)
J. Biol. Chem.
283, 4578-4587
|Abstract »|Full Text »|PDF »
DNA inhibits catalysis by the carboxyltransferase subunit of acetyl-CoA carboxylase: Implications for active site communication.
B. K. Benson, G. Meades Jr, A. Grove, and G. L. Waldrop (2008)
Protein Sci.
17, 34-42
|Abstract »|Full Text »|PDF »
Bach1 Repression of Ferritin and Thioredoxin Reductase1 Is Heme-sensitive in Cells and in Vitro and Coordinates Expression with Heme Oxygenase1, beta-Globin, and NADP(H) Quinone (Oxido) Reductase1.
K. J. Hintze, Y. Katoh, K. Igarashi, and E. C. Theil (2007)
J. Biol. Chem.
282, 34365-34371
|Abstract »|Full Text »|PDF »
RsmA Is an Anti-sigma Factor That Modulates Its Activity through a [2Fe-2S] Cluster Cofactor.
A. A. Gaskell, J. C. Crack, G. H. Kelemen, M. I. Hutchings, and N. E. Le Brun (2007)
J. Biol. Chem.
282, 31812-31820
|Abstract »|Full Text »|PDF »
Yeast aconitase binds and provides metabolically coupled protection to mitochondrial DNA.
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. 
