Transferrin (iron transport protein) receptor (TfR) protein
Homo sapiens (human)
Iron is an essential element of nutrition and human biochemistry. Iron is transported through the body by molecules called transferrins. Although being small, getting inside a cell is not so easy for iron, because cells are surrounded by membranes. Passing charged elements like iron through such membranes requires special tricks. One way to accomplish that are ion channels, often used for the likes of sodium, potassium or calcium. Another method is endocytosis for entering the cell or exocytosis for leaving it. Part of the cell membrane surrounds the material to be imported, dissociates from the rest of the membrane and forms a particle called endosome which is released into the cell. Iron uses this type of import mechanism. Transferrin, with bound iron, arriving near a cell, is recognized by another molecule, the transferrin receptor (TfR). The receptor protein is partly embedded into the cell membrane. Transferrin is tightly bound to its receptor and the whole complex passes through the membrane into the cell by endocytosis. This particular type of endocytosis is called receptor-mediated endocytosis. Once the complex is inside the cell, pH changes within the endosome cause transferrin to release the iron and the transferrin, still bound to its receptor, returns to the cell surface and is expelled from the cell by exocytosis. As the complex, now containing transferrin without iron, reaches the extracellular space, transferrin is released from the receptor. Considering that transferrin is a molecule containing about 6,000 atoms and that the receptor is a molecule with about 6,500 atoms, this is surely a very involved way to move one atom, iron, across a membrane.
Human TfR is a homodimeric type II transmembrane protein. The TfR monomer contains three distinct domains, the protease-like domain, the apical domain, and the helical domain.
Protein Data Bank (PDB)
author: Arno Paehler