Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing.
HFE and transferrin receptor 2 (TFR2) are membrane proteins integral to mammalian iron homeostasis and associated with human hereditary hemochromatosis. Here we demonstrate that HFE and TFR2 interact in cells, that this interaction is not abrogated by disease-associated mutations of HFE and TFR2, and that TFR2 competes with TFR1 for binding to HFE. We propose a new model for the mechanism of iron status sensing that results in the regulation of iron homeostasis.
Goswami
Tapasree
T
Harvard Medical School, Children's Hospital Boston, Division of Hematology/Oncology and Howard Hughes Medical Institute, Boston, Massachusetts 02115-5737, USA.
Andrews
Nancy C
NC
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D006432:Hemochromatosis / Q000235:genetics; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D011990:Receptors, Transferrin / Q000378:metabolism / Q000502:physiology*
D015703:Antigens, CD; C068126:CD71 antigen; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; C503641:TFR2 protein, mouse; C480029:Tfrc protein, mouse; D007501:Iron