A Comprehensive Review of Our Current Understanding of Red Blood Cell (RBC) Glycoproteins (1)
The typical human red blood cell membrane proteins were separated by SDS-PAGE. The nomenclature of each cell membrane protein, along with apparent molecular mass (kDa) and physiological function. Band 3, band 4.1, and band 4.2 are called the designated names at present. Band 3 is a glycoprotein and is detected as a diffuse band on SDS gel due to the microheterogeneity of the attached oligosaccharides.
The nomenclature of human red cell membrane sialoglycoproteins was shown.The glycophorins were called as PAS 1–4 and, at present, they are termed glycophorins A–D, respectively. Glycophorin α is the same as glycophorin A, and glycophorin δ, β, and γ are glycophorins B, C, and D, respectively. Glycophorin A (dimer) is observed below band 3 on SDS-polyacrylamide gels, is a major component of red cell membrane glycoproteins, and is reported to have an apparent molecular mass of 29 to 36 kDa.
Band 3 and glycophorins are transmembrane proteins. Transmembrane proteins are associated with the peripheral proteins that constitute the protein meshwork (cytoskeleton). The main component of the cytoskeleton is a spectrin tetramer. Its ends are linked by binding to the actin filament and band 4.1, and it forms a junctional complex. These junctions are linked to the end of some spectrin tetramers and form a netlike meshwork. The band 3 protein is the most abundant of the red cell membrane proteins and composes approximately 25% of these proteins. For Band 3, approximately 1.0 × 10^6 copies are present in each red blood cell. The molecular mass of band 3 is estimated at approximately 100 kDa by SDS-PAGE.
Band 3 is composed of amino peptides and a single N-linked oligosaccharide, and the molecular mass of the carbohydrate is approximately 8% of band 3. This N-linked oligosaccharide is linked at Asn-649, which is located at a site approximately 28 amino acids from the C-terminus of the band 3 polypeptide. This oligosaccharide is exposed on the external side of the membrane and is heterogeneous in size on different band 3 molecules, as determined by the number of repeating N-acetyllactosamine units (Galβ1→4 GlcNAcβ1→3). The end of the band 3 oligosaccharide is linked to sialic acid. This sialic acid is N-acetylneuraminic acid (5-acetamido-3,5-dideoxy-α-d-glycero-d-galacto-2-nonulopyranosidonic acid; Neu5Ac, NeuAc, NANA) and occurs broadly in humans. Band 3 is well known to function as an anion exchanger. When red blood cells pass through the lung blood vessels, band 3 protein has a function in collecting CO2 from human tissues in exchange for Cl− as the form of HCO3−. The localization of band 3 changes to bind anti-band 3 IgG (senescent antigen). The anti-band 3 IgG that binds band 3 is recognized in the spleen by macrophages, and macrophage autolysis digests the senescent red blood cell.
1. T. Aoki, A Comprehensive Review of Our Current Understanding of Red Blood Cell (RBC) Glycoproteins. Membranes . 7 (2017), doi:10.3390/membranes7040056.