Structure of Dual Function Iron Regulatory Protein 1 Complexed with Ferritin IRE-RNA
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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Tài liệu tham khảo
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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).