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Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor.
Lebrón, J A; Bennett, M J; Vaughn, D E; Chirino, A J; Snow, P M; Mintier, G A; Feder, J N; Bjorkman, P J.
Afiliación
  • Lebrón JA; Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Cell ; 93(1): 111-23, 1998 Apr 03.
Article en En | MEDLINE | ID: mdl-9546397
HFE is an MHC-related protein that is mutated in the iron-overload disease hereditary hemochromatosis. HFE binds to transferrin receptor (TfR) and reduces its affinity for iron-loaded transferrin, implicating HFE in iron metabolism. The 2.6 A crystal structure of HFE reveals the locations of hemochromatosis mutations and a patch of histidines that could be involved in pH-dependent interactions. We also demonstrate 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.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Transferrina / Antígenos de Histocompatibilidad Clase I / Estructura Secundaria de Proteína / Antígenos HLA / Proteínas de la Membrana Límite: Humans Idioma: En Revista: Cell Año: 1998 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Transferrina / Antígenos de Histocompatibilidad Clase I / Estructura Secundaria de Proteína / Antígenos HLA / Proteínas de la Membrana Límite: Humans Idioma: En Revista: Cell Año: 1998 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos