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

被引：147

作者：

Lebrón, JA

West, AG

Bjorkman, PJ

机构：

[1] CALTECH, Div Biol 15629, Pasadena, CA 91125 USA

[2] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA

来源：

JOURNAL OF MOLECULAR BIOLOGY | 1999年 / 294卷 / 01期

关键词：

HFE; inhibition; class I MHC homolog; iron overload; surface plasmon resonance;

D O I：

10.1006/jmbi.1999.3252

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

HFE is a class I major histocompatibility complex (MHC)-related protein that is mutated in patients with the iron overload disease hereditary hemochromatosis. HFE binds to transferrin receptor (TfR), the receptor used by cells to obtain iron in the form of diferric transferrin (Fe-Tf). Previous studies 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 surface TfR results in a reduction in the affinity of TfR for Fe-Tf. We studied the inhibition by soluble HFE of the interaction between soluble TfR and Fe-Tf using radioactivity-based and biosensor-based assays. The results demonstrate that HFE inhibits the TfR:Fe-Tf interaction by binding at or near 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 Academic Press.

引用

页码：239 / 245

页数：7

共 22 条

[1] Iron metabolism [J].

Aisen, P ;

Wessling-Resnick, M ;

Leibold, EA .

CURRENT OPINION IN CHEMICAL BIOLOGY, 1999, 3 (02) :200-206

[2] Control of iron absorption [J].

Anderson, GJ .

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 1996, 11 (11) :1030-1032

[3]

BENNETT MJ, 1999, IN PRESS NATURE

[4] CRYSTALLIZATION AND X-RAY-DIFFRACTION STUDIES OF A SOLUBLE FORM OF THE HUMAN TRANSFERRIN RECEPTOR [J].

BORHANI, DW ;

HARRISON, SC .

JOURNAL OF MOLECULAR BIOLOGY, 1991, 218 (04) :685-689

[5]

CREIGHTON TE, 1993, PROTEINS STRUCTURES, P389

[6]

ENNS CA, 1981, J BIOL CHEM, V256, P9820

[7] The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding [J].

Feder, JN ;

Penny, DM ;

Irrinki, A ;

Lee, VK ;

Lebrón, JA ;

Watson, N ;

Tsuchihashi, Z ;

Sigal, E ;

Bjorkman, PJ ;

Schatzman, RC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (04) :1472-1477

[8] A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis [J].

Feder, JN ;

Gnirke, A ;

Thomas, W ;

Tsuchihashi, Z ;

Ruddy, DA ;

Basava, A ;

Dormishian, F ;

Domingo, R ;

Ellis, MC ;

Fullan, A ;

Hinton, LM ;

Jones, NL ;

Kimmel, BE ;

Kronmal, GS ;

Lauer, P ;

Lee, VK ;

Loeb, DB ;

Mapa, FA ;

McClelland, E ;

Meyer, NC ;

Mintier, GA ;

Moeller, N ;

Moore, T ;

Morikang, E ;

Prass, CE ;

Quintana, L ;

Starnes, SM ;

Schatzman, RC ;

Brunke, KJ ;

Drayna, DT ;

Risch, NJ ;

Bacon, BR ;

Wolff, RK .

NATURE GENETICS, 1996, 13 (04) :399-408

[9] The hemochromatosis founder mutation in HLA-H disrupts beta(2)-microglobulin interaction and cell surface expression [J].

Feder, JN ;

Tsuchihashi, Z ;

Irrinki, A ;

Lee, VK ;

Mapa, FA ;

Morikang, E ;

Prass, CE ;

Starnes, SM ;

Wolff, RK ;

Parkkila, S ;

Sly, WS ;

Schatzman, RC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (22) :14025-14028

[10] Co-trafficking of HFE, a nonclassical major histocompatibility complex class I protein, with the transferrin receptor implies a role in intracellular iron regulation [J].

Gross, CN ;

Irrinki, A ;

Feder, JN ;

Enns, CA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (34) :22068-22074

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