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

Lebrón, José A. and West, Anthony P., Jr. and Bjorkman, Pamela J. (1999) The hemochromatosis protein HFE competes with transferrin for binding to the transferrin receptor. Journal of Molecular Biology, 294 (1). pp. 239-245. ISSN 0022-2836. doi:10.1006/jmbi.1999.3252.

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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.

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Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 1999 Academic Press. Received 25 August 1999, Revised 28 September 1999, Accepted 28 September 1999. We thank members of the Bjorkman lab for critical reading of the manuscript and M. J. Bennett and A. Townsend for helpful discussions. J.A.L. was supported by an NIH/NRSA training grant (#GM07616) and A.P.W. was supported by a post-doctoral fellowship from the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation (DRG #1445). This work was supported by the Howard Hughes Medical Institute and a grant from the Arthritis Foundation (P.J.B.).
Funding AgencyGrant Number
NIH Predoctoral FellowshipGM07616
Damon Runyon-Walter Winchell FoundationDRG 1445
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Arthritis FoundationUNSPECIFIED
Subject Keywords:HFE; inhibition; class I MHC homolog; iron overload; surface plasmon resonance
Issue or Number:1
Record Number:CaltechAUTHORS:20170406-074901050
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Official Citation:José A Lebrón, Anthony P West Jr, Pamela J Bjorkman, The hemochromatosis protein HFE competes with transferrin for binding to the transferrin receptor1, Journal of Molecular Biology, Volume 294, Issue 1, 19 November 1999, Pages 239-245, ISSN 0022-2836, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75776
Deposited By: Tony Diaz
Deposited On:06 Apr 2017 16:45
Last Modified:15 Nov 2021 16:36

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