Structure of dual function iron regulatory protein 1 complexed with ferritin IRE-RNA

Science. 2006 Dec 22;314(5807):1903-8. doi: 10.1126/science.1133116.

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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Apoferritins / genetics*
  • Binding Sites
  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Iron / metabolism
  • Iron Regulatory Protein 1 / chemistry*
  • Iron Regulatory Protein 1 / metabolism*
  • Models, Molecular
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Regulatory Sequences, Ribonucleic Acid*
  • Response Elements*
  • Sulfur / metabolism
  • Untranslated Regions / chemistry*
  • Untranslated Regions / metabolism*

Substances

  • RNA, Messenger
  • Regulatory Sequences, Ribonucleic Acid
  • Untranslated Regions
  • Sulfur
  • Apoferritins
  • Iron
  • Iron Regulatory Protein 1

Associated data

  • PDB/2IPY