| Structures of the oligosaccharides attached to proteins
|
Sugars are linked to each other in glycosidic linkages. Two identical hexose residues can be linked together in many different ways (α1,2; α1,3; α1,4; α1,6; β1,2; β1,3; β1,4; β1,6), yielding distinct disaccharides; in contrast, two identical amino acids can only be combined in one way - two alanine residues can form only one dipeptide, alanyl-alanine. Thus carbohydrate structures have greater structural diversity, and therefore have the potential to contain more information than proteins of similar size. Nevertheless, although there are a large number of structures produced by living cells, most of the oligosaccharides on glycoconjugates have many sugars and linkages in common.
|
| N-linked oligosaccharides have either 'high-mannose' or 'complex' structures built on to a common core of mannose and GlcNAc
|
| All the N-linked oligosaccharide chains that are found on proteins are, typically, branched structures having a common core structure of two GlcNAc and three mannose residues (shown by the boxed areas in Fig. 25.3). Beyond this core region, the oligosaccharides can be very different from each other, giving rise to a vast array of structures. Thus, oligosaccharides may be either 'high-mannose' structures containing only two GlcNAc residues and up to nine mannose units (Fig. 25.3A), or they may consist of 'complex' chains (Fig. 25.3B), so named because of their more complex composition. All the N-linked chains are initially assembled as the high-mannose structure, which is then modified to give rise to different types of complex oligosaccharides. High-mannose oligosaccharides are found to a limited extent in animal glycoproteins; they are more common in glycoproteins of lower eukaryotes and in viral envelope glycoproteins. Complex oligosaccharides are common in animals, but are generally not present in lower eukaryotes.
|
| page 360 |  | | page 361 |
| Figure 25.2 Various linkages of sugars to amino acids in glycoproteins. GlcNAc, N-acetylglucosamine. |
| Complex oligosaccharides have the same core structure as the high-mannose oligosaccharides, but have terminal trisaccharide sequences composed of sialic acid-galactose-GlcNAc attached to the core mannose structure. Fucose may be found in the core (see Fig. 25.1A) or in place of sialic acid in complex oligosaccharides. In common with sialic acid, fucose is usually a terminal sugar on oligosaccharides - that is, no other sugars are attached to it. Some complex oligosaccharides have two of the terminal trisaccharide sequences (one
attached to each mannose) and are called 'biantennary' complex chains, whereas others have trior tetra-antennary structures (Fig. 25.3B). 'Microheterogeneity' of oligosaccharide structure results from the fact that the basic structure is often found in an incomplete form on glycoproteins, e.g. a missing terminal sialic acid or sialyl-galactose residues on one or more of the antennae. A given glycoprotein may also have several N-linked oligosaccharides and these may have the same or different types of antennary structures. Generally, oligosaccharides located near the amino terminus are more highly processed (complex types) whereas those near the carboxy terminus are more likely to be high-mannose types. More than 100 different complex oligosaccharide structures have now been identified, giving carbohydrates great diversity as mediators of chemical signaling and recognition events.
|
| The viscous properties of mucins derive from their content of negatively charged sialic acid
|
| In mucins, the O-linked oligosaccharides are usually short, branched structures containing sialic acid (N-acetylneuraminic acid), galactose, and GalNAc, and sometimes other sugars such as GlcNAc and l-fucose (Fig. 25.4). Salivary mucin contains an unusually large number of serine or threonine residues, and many of these serines or threonines are glycosylated with a sialic acid-galactose-GalNAc trisaccharide. The O-linked oligosaccharides are negatively charged because of the presence of the sialic acid residues, and when they occur in clusters and in close proximity to each other, they repel each other and prevent the protein from folding. As a result, the protein assumes an extended state, yielding a highly viscous (mucous) solution. Mucins form a protective barrier on the surface of epithelial cells, provide lubrication between surfaces, and facilitate transport processes - for example, the movement of food through the gastrointestinal tract.
|
|
