Article

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

Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Cell (Impact Factor: 33.12). 05/1998; 93(1):111-23. DOI: 10.1016/S0092-8674(00)81151-4
Source: PubMed

ABSTRACT 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.

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