Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor
Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor
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DOI：
10.1016/s0092-8674(00)81151-4
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发表时间：
1998-04-03
期刊：
影响因子：
64.5
通讯作者：
Bjorkman, PJ
中科院分区：
文献类型：
--
作者：
Lebrón, JA;Bennett, MJ;Bjorkman, PJ
HFE是一种MHC相关蛋白，在铁超负荷疾病遗传性血色病中发生突变。HFE与转铁蛋白受体（TfR）结合，并降低其对铁载转铁蛋白的亲和力，表明HFE参与铁代谢。HFE的2.6埃晶体结构揭示了血色病突变的位置和可能参与pH依赖性相互作用的组氨酸补丁。我们还表明，可溶性TfR和HFE紧密结合在细胞表面的碱性pH值，但不是在细胞内囊泡的酸性pH值。TfR：HFE化学计量（2：1）不同于TfR：HFE化学计量（2：1）。转铁蛋白化学计量比（2：2），这意味着HFE和转铁蛋白与TfR的不同结合模式，与我们证明的HFE、转铁蛋白和TfR形成三元复合物一致。
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 Angstrom 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.