Protein architecture of the erythrocyte membrane

The normal human erythrocyte is comprised of as many as 90 polypeptides. These membrane polypeptides are organized asymmetrically within the membrane. In a well-washed erythrocyte, all the polypeptides exposed on the outside surface are transmembrane proteins. Six such polypeptides have been identified. They are the anion transport component protein 3, the glucose transport protein 4.5 and the sialoglycoproteins PAS 1, 2', 2 and 3. The major membrane protein, protein 3, which comprises 25% of the total membrane peptide, interacts on the cytoplasmic surface with the cytoskeletal components. The sialoglycoprotein PAS 2 has also been shown to interact with cytoskeleton and has been named glycoconnectin. Employing a monolayer freeze-fracture technique, the transmembrane proteins have been shown to distribute asymmetrically. For example, the major sialoglycoproteins distribute with the outer half of the bilayer (E-face) while protein 3 is found exclusively on the inner half of the bilayer (P-face). The anchoring of the transmembrane proteins determines on which half of the bilayer the protein will be found. Well-defined fragments of the sialoglycoprotein are produced by the freeze-fracture procedure indicating that selected covalent bonds of these transmembrane proteins were broken. Correlation of these results with the appearance of intramembrane particles on the E- and P-faces indicate that protein 3 may account for most of the intramembrane particles found on the P-face, while the sialoglycoproteins probably account for little, if any, of the particles. Although the evidence is not conclusive, protein 4.5 may account for the particles on the E-face of the freeze-fractured human erythrocyte membrane.