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Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor.

HFE is an MHC-related protein that is mutated in the iron-overload disease hereditary hemochromatosis. HFE binds to transferrin receptor (TfR) and reduces its affinity for iron-loaded transferrin, implicating HFE in iron metabolism. The 2.6 A crystal structure of HFE reveals the locations of hemochromatosis mutations and a patch of histidines that could be involved in pH-dependent interactions. We also demonstrate that soluble TfR and HFE bind tightly at the basic pH of the cell surface, but not at the acidic pH of intracellular vesicles. TfR:HFE stoichiometry (2:1) differs from TfR:transferrin stoichiometry (2:2), implying a different mode of binding for HFE and transferrin to TfR, consistent with our demonstration that HFE, transferrin, and TfR form a ternary complex.

Pubmed ID: 9546397


  • Lebrón JA
  • Bennett MJ
  • Vaughn DE
  • Chirino AJ
  • Snow PM
  • Mintier GA
  • Feder JN
  • Bjorkman PJ



Publication Data

April 3, 1998

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Binding Sites
  • Cell Membrane
  • Crystallography, X-Ray
  • HLA Antigens
  • Hemochromatosis
  • Histocompatibility Antigens Class I
  • Humans
  • Hydrogen-Ion Concentration
  • Kinetics
  • Membrane Proteins
  • Models, Molecular
  • Protein Structure, Secondary
  • Receptors, Transferrin