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

American Association for the Advancement of Science (AAAS) - Tập 314 Số 5807 - Trang 1903-1908 - 2006
William E. Walden1,2,3, Anna I. Selezneva1,2,3, Jérôme Dupuy1,2,3, Anne Volbeda1,2,3, Juan C. Fontecilla‐Camps1,2,3, Elizabeth C. Theil1,2,3, Karl Volz1,2,3
1Children'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.
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612–7344, USA.
3Laboratoire 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.

Tóm tắt

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.

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Single-letter abbreviations for the amino acid residues are as follows: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; and Y Tyr.

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Supported by grants from the National Institutes of Health (DK47281 to W.E.W. DK20251 to E.C.T. and GM47522 to K.V.). We thank E. A. Craig R. S. Eisenstein H. Noller T. A. Steitz and D. S. Ucker for critical review of the manuscript. Data were collected at the Southeast regional collaborative access team (SER-CAT) 22-ID at the Advanced Photon Source Argonne National Laboratory. Use of the Advanced Photon Source was supported by the Department of Energy under contract No. W-31-109-Eng-38. Structure factors and coordinates have been deposited in the Protein Data Bank (accession code 2IPY).

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American Association for the Advancement of Science (AAAS)

Tập 314 Số 5807

1903-1908

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