Molecular dissection of the human transferrin receptor.

Transferrin is the major iron carrier protein in vertebrates and is required for maintenance of cell viability. To deliver iron, transferrin binds to its receptor, the complex is internalized and directed into acidic vacuoles where iron is dissociated and the ligand-receptor complex is recycled back to the plasma membrane. The transferrin receptor is a transmembrane glycoprotein, composed of two disulphide-bonded subunits (each of apparent Mr 90 000). It contains three N-linked glycan units and is post-translationally modified with both phosphate and fatty-acyl groups. The primary structure of the receptor consists of 760 amino acids divided into three domains. Starting from the N-terminal residue the cytoplasmic domain consists of 62 amino acids, followed by 26 predominantly non-polar residues, which constitute the transmembrane domain, and 672 residues form the C-terminal extracellular domain. It does not contain an N-terminal cleavable signal sequence.