Structure of dual function iron regulatory protein 1 complexed with ferritin IRE-RNA.
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 approximately 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.
Walden
William E
WE
Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612-7344, USA.
Selezneva
Anna I
AI
Dupuy
Jérôme
J
Volbeda
Anne
A
Fontecilla-Camps
Juan C
JC
Theil
Elizabeth C
EC
Volz
Karl
K
D001052:Apoferritins / Q000235:genetics*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D007501:Iron / Q000378:metabolism; D035941:Iron Regulatory Protein 1 / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D020218:Response Elements; D013455:Sulfur / Q000378:metabolism; D020506:Untranslated Regions / Q000737:chemistry* / Q000378:metabolism*
D012333:RNA, Messenger; D038621:Regulatory Sequences, Ribonucleic Acid; D020506:Untranslated Regions; D013455:Sulfur; D001052:Apoferritins; D007501:Iron; D035941:Iron Regulatory Protein 1