Ja. Lebron et al., CRYSTAL-STRUCTURE OF THE HEMOCHROMATOSIS PROTEIN HFE AND CHARACTERIZATION OF ITS INTERACTION WITH TRANSFERRIN RECEPTOR, Cell, 93(1), 1998, pp. 111-123
HFE is an MHC-related protein that is mutated in the iron-overload dis
ease hereditary hemochromatosis. HFE binds to transferrin receptor (Tf
R) and reduces its affinity for iron-loaded transferrin, implicating H
FE in iron metabolism. The 2.6 Angstrom crystal structure of HFE revea
ls the locations of hemochromatosis mutations and a patch of histidine
s that could be involved in pH-dependent interactions. We also demonst
rate 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.