CRYSTAL-STRUCTURE OF THE HEMOCHROMATOSIS PROTEIN HFE AND CHARACTERIZATION OF ITS INTERACTION WITH TRANSFERRIN RECEPTOR

Citation
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
Citations number
50
Categorie Soggetti
Biology,"Cell Biology
Journal title
CellACNP
ISSN journal
00928674
Volume
93
Issue
1
Year of publication
1998
Pages
111 - 123
Database
ISI
SICI code
0092-8674(1998)93:1<111:COTHPH>2.0.ZU;2-S
Abstract
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.