Harpers

GLYCOPROTEINS / 519AOHCHCH 2 OHCHOHCHHC NH 2CH 3Ethanolamine P MannoseOαProteinHC O CH 2 CGlycineHCSerEthanolamineNPC OMannoseMannoseBCH 2 OHGlucosamineHCHOCOHCOHCH HβOC N CAsnCH 2CPI-PLCPInositolAdditional fatty acidPlasmamembraneHHNCCH 3OFigure 47–1. Depictions of (A) an O-linkage (N-acetylgalactosamine to serine); (B) an N-linkage (N-acetylglucosamineto asparagine) and (C) a glycosylphosphatidylinositol (GPI) linkage. The GPI structure shown is thatlinking acetylcholinesterase to the plasma membrane of the human red blood cell. The carboxyl terminal aminoacid is glycine joined in amide linkage via its COOH group to the NH 2 group of phosphorylethanolamine, whichin turn is joined to a mannose residue. The core glycan contains three mannose and one glucosamine residues.The glucosamine is linked to inositol, which is attached to phosphatidic acid. The site of action of PI-phospholipaseC (PI-PLC) is indicated. The structure of the core glycan is shown in the text. This particular GPI contains anextra fatty acid attached to inositol and also an extra phosphorylethanolamine moiety attached to the middle ofthe three mannose residues. Variations found among different GPI structures include the identity of the carboxylterminal amino acid, the molecules attached to the mannose residues, and the precise nature of the lipid moiety.ANeuAcBGalα 2,6β 1,3α 2,3NeuAcGalNAcGalNAcα 2,6NeuAcSer(Thr)Ser(Thr)Figure 47–2. Structures of two O-linked oligosaccharidesfound in (A) submaxillary mucins and (B) fetuinand in the sialoglycoprotein of the membrane ofhuman red blood cells. (Modified and reproduced, withpermission, from Lennarz WJ: The Biochemistry of Glycoproteinsand Proteoglycans. Plenum Press, 1980.)Mucins Have a High Content of O-LinkedOligosaccharides & Exhibit RepeatingAmino Acid SequencesMucins are glycoproteins with two major characteristics:(1) a high content of O-linked oligosaccharides(the carbohydrate content of mucins is generally morethan 50%); and (2) the presence of repeating aminoacid sequences (tandem repeats) in the center of theirpolypeptide backbones, to which the O-glycan chainsare attached in clusters (Figure 47–3). These sequencesare rich in serine, threonine, and proline. Although O-glycans predominate, mucins often contain a numberof N-glycan chains. Both secretory and membraneboundmucins occur. The former are found in themucus present in the secretions of the gastrointestinal,respiratory, and reproductive tracts. Mucus consists ofabout 94% water and 5% mucins, with the remainder