The hemochromatosis protein HFE competes with transferrin for binding to the transferrin receptor

Citation
Ja. Lebron et al., The hemochromatosis protein HFE competes with transferrin for binding to the transferrin receptor, J MOL BIOL, 294(1), 1999, pp. 239-245
Citations number
22
Categorie Soggetti
Molecular Biology & Genetics
Journal title
JOURNAL OF MOLECULAR BIOLOGY
ISSN journal
00222836 → ACNP
Volume
294
Issue
1
Year of publication
1999
Pages
239 - 245
Database
ISI
SICI code
0022-2836(19991119)294:1<239:THPHCW>2.0.ZU;2-0
Abstract
HFE is a class I major histocompatibility complex (MHC)-related protein tha t is mutated in patients with the iron overload disease hereditary hemochro matosis. HFE binds to transferrin receptor (TfR), the receptor used by cell s to obtain iron in the form of diferric transferrin (Fe-Tf). Previous stud ies demonstrated that HFE and Fe-Tf can bind simultaneously to TfR to form a ternary complex, and that membrane-bound or soluble HFE binding to cell s urface TfR results in a reduction in the affinity of TfR for Fe-Tf. We stud ied the inhibition by soluble HFE of the interaction between soluble TfR an d Fe-Tf using radioactivity-based and biosensor-based assays. The results d emonstrate that HFE inhibits the TfR:Fe-Tf interaction by binding at or nea r the Fe-Tf binding site on TfR, and that the Fe-Tf:TfR:HFE ternary complex consists of one Fe-Tf and one HFE bound to a TfR homodimer. (C) 1999 Acade mic Press.