Structure of the human transferrin receptor-transferrin complex
Structure of the human transferrin receptor-transferrin complex
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DOI：
10.1016/s0092-8674(04)00130-8
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发表时间：
2004-02-20
期刊：
影响因子：
64.5
通讯作者：
Walz, T
中科院分区：
文献类型：
--
作者：
Cheng, Y;Zak, O;Walz, T
铁以游离Fe3+的形式不溶，以游离Fe2+的形式有毒，以Fe3+与转铁蛋白(Tf)结合的形式分布在体内，通过与转铁蛋白受体(TfR)的络合物内吞进入细胞。尽管人们对转铁蛋白内吞周期了解很多，但对受体-转铁蛋白复合体形成的分子细节却知之甚少。使用冷冻电子显微镜，我们已经在亚纳米分辨率下绘制了TFR-Tf络合物的密度图。通过将二铁Tf和受体胞外结构域的晶体结构拟合得到的原子模型表明，Tf N叶夹在膜和TFR胞外结构域之间，C叶毗邻受体螺旋结构域。当Tf与受体结合时，其N叶相对于C叶移动约9埃。转铁蛋白受体-转铁蛋白复合体的结构有助于解释游离转铁蛋白和受体结合转铁蛋白的铁释放特性的已知差异。
Iron, insoluble as free Fe3+ and toxic as free Fe2+, is distributed through the body as Fe3+ bound to transferrin (Tf) for delivery to cells by endocytosis of its complex with transferrin receptor (TfR). Although much is understood of the transferrin endocytotic cycle, little has been uncovered of the molecular details underlying the formation of the receptor-transferrin complex. Using cryo-electron microscopy, we have produced a density map of the TfR-Tf complex at subnanometer resolution. An atomic model, obtained by fitting crystal structures of diferric Tf and the receptor ectodomain into the map, shows that the Tf N-lobe is sandwiched between the membrane and the TfR ectodomain and that the C-lobe abuts the receptor helical domain. When Tf binds receptor, its N-lobe moves by about 9 Angstrom with respect to its C-lobe. The structure of TfR-Tf complex helps account for known differences in the iron-release properties of free and receptor bound Tf.