1A6Z

HFE (HUMAN) HEMOCHROMATOSIS PROTEIN

Summary for 1A6Z

• Entry DOI: 10.2210/pdb1a6z/pdb
• Descriptor: HFE, BETA-2-MICROGLOBULIN (3 entities in total)
• Functional Keywords: hfe, hereditary hemochromatosis, mhc class i, mhc class i complex
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane ; Single-pass type I membrane protein : Q30201; Secreted . Note=(Microbial infection) In the presence of M: P61769
• Total number of polymer chains: 4
• Total formula weight: 88175.19

Authors

Lebron, J.A.,Bennett, M.J.,Vaughn, D.E.,Chirino, A.J.,Snow, P.M.,Mintier, G.A.,Feder, J.N.,Bjorkman, P.J. (deposition date: 1998-03-04, release date: 1999-03-23, Last modification date: 2024-10-30)

Primary citation

Lebron, J.A.,Bennett, M.J.,Vaughn, D.E.,Chirino, A.J.,Snow, P.M.,Mintier, G.A.,Feder, J.N.,Bjorkman, P.J.
Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor.
Cell(Cambridge,Mass.), 93:111-123, 1998

PubMed Abstract: 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.

PubMed: 9546397
DOI: 10.1016/S0092-8674(00)81151-4

Experimental method

X-RAY DIFFRACTION (2.6 Å)