Glycoproteins are proteins to which oligosaccharides (glycans) are covalently attached. [Note: Glycosylation is the most common posttranslational modification of proteins.] They differ from the proteoglycans in several important ways. Glycoproteins contain highly variable amounts of carbohydrate but typically less than that of proteoglycans. For example, the glycoprotein immunoglobulin G (IgG) contains <4% of its mass as carbohydrate, whereas the proteoglycan aggrecan contains >80%. In glycoproteins, the glycan is relatively short (usually two to ten sugar residues in length, although it can be longer); does not contain repeating disaccharide units and, consequently, is structurally diverse; is often branched instead of linear; and may or may not be negatively charged. Membrane-bound glycoproteins participate in a broad range of cellular phenomena, including cell-surface recognition (by other cells, hormones, and viruses), cell-surface antigenicity (such as the blood group antigens), and as components of the ECM and of the mucins of the gastrointestinal and urogenital tracts, where they act as protective biologic lubricants. In addition, almost all of the globular proteins present in human plasma are glycoproteins, although albumin is an exception. Figure 14.13 summarizes some glycoprotein functions.
VII. OLIGOSACCHARIDE STRUCTURE
The oligosaccharide (glycan) components of glycoproteins are generally branched heteropolymers composed primarily of D-hexoses, with the addition in some cases of neuraminic acid (a nonose) and of L-fucose, a 6-deoxyhexose.
A. Carbohydrate–protein linkage
The glycan may be attached to the protein through an N-or an O-glycosidic link (see p. 86). In the former case, the sugar chain is attached to the amide group of an asparagine side chain and, in the latter case, to the hydroxyl group of either a serine or threonine side chain. [Note: In the case of collagen, there is an O-glycosidic linkage between galactose or glucose and the hydroxyl group of hydroxylysine (see p. 47).]
B. N-and O-Linked oligosaccharides
A glycoprotein may contain only one type of glycosidic linkage (N or O linked) or may have both types within the same molecule.
1.
O-Linked: The O-linked glycans may have one or more of a wide variety of sugars arranged in either a linear or a branched pattern. Many are found in extracellular glycoproteins or as membrane glycoprotein components. For example, O-linked oligosaccharides on the surface of red blood cells help provide the ABO blood group determinants. If the terminal sugar on the glycan is GalNAc, the blood group is A. If it is galactose, the blood group is B. If neither GalNAc nor galactose is present, the blood group is O.
2.
N-Linked: The N-linked glycans fall into two broad classes: complex oligosaccharides and high-mannose oligosaccharides. Both contain the same pentasaccharide core shown in Figure 14.14, but the complex oligosaccharides contain a diverse group of additional sugars, for example, GlcNAc, GalNAc, L-fucose, and NANA, whereas the high mannose oligosaccharides contain primarily mannose.
VIII. GLYCOPROTEIN SYNTHESIS