Question

Explain briefly how oligosaccharides function as cell markers.

Answer 1

Oligosaccharide:

An oligosaccharide is a saccharide polymer containing a small number (typically two to ten) of simple sugars. Oligosaccharides can have many functions including cell recognition and cell binding. For example, glycolipids have an important role in the immune response.

In general, they are found either N- or O-linked to compatible amino acid side-chains in proteins or to lipid moieties. N-linked oligosaccharides are found attached to asparagine via a beta linkage to the amine nitrogen of the side chain. Alternately, O-linked oligosaccharides are generally attached to threonine or serine on the alcohol group of the side chain.

Glycosylation:

In biology, glycosylation is the co-translational process by which a carbohydrate is covalently attached to an organic molecule – creating structures such as glycoproteins and glycolipids.

N-linked Oligosaccharides:

An example of N-linked oligosaccharides

N-linked glycosylation involves oligosaccharide attachment to asparagine via a beta linkage to the amine nitrogen of the side chain. The process of N-linked glycosylation occurs cotranslationally, or concurrently while the proteins is being translated. Since it is added cotranslationally, it is believed that N-linked glycosylation helps determine the folding of polypeptides due to the hydrophilic nature of sugars. All N-linked Oligosaccharides are composed of a core of five sugars - known as a pentasaccharide.

In N-glycosylation for eukaryotes, the oligosaccharide substrate is assembled right at the membrane of the ER. For prokaryotes, this process occurs at the plasma membrane. In both cases, the acceptor substrate is asparagine residue. They are small carbohydrates which are formed by condensation of 2-9 monosacchrides. This asparagine has increased nucleophilicity in the amide group. The unique arrangement of N-linked oligosaccharides usually has the oligosaccharide linked to the amide nitrogen of the Asn residue, in the sequence Asn-X-Ser/Thr. X can be any amino acid except for proline (though it is rare to see Asp, Glu, Leu, or Trp).

O-linked Oligosaccharides:

An example of O-linked oligosaccharides

Oligosaccharides that participate in O-linked glycosylation are attached to threonine or serine on the alcohol group of the side chain. O-linked glycosylation occurs in the golgi apparatus, in which monosaccharide units are added to a complete polypeptide chain. Cell surface proteins and extracellular proteins are O-glycosylated. Glycosylation sites in O-linked oligosaccharides are specified only in the secondary and tertiary structures of the polypeptide, which will dictate where glycosyltransferases will add sugars.

Functions:

Cell Recognition:

All cells are coated in either glycoproteins or glycolipids, both of which help determine cell types. Lectins, or proteins that bind carbohydrates, which can recognize very specific oligosaccharides and provide useful information for cell recognition due to oligosaccharide binding.

An important example of oligosaccharide cell recognition is the role of glycolipids in determining blood types. The various blood types are distinguished by the glycan modification present on the surface of blood cells. These can be visualized using mass spectrometry. The oligosaccharides found on the A, B, and H antigen occurs on the non-reducing ends of the oligosaccharide. The H antigen (which indicates an O blood type) serves as a precursor for the A and B antigen. Therefore, a person with A blood type will have the A antigen and H antigen present on the glycolipids of the red blood cell plasma membrane. A person with B blood type will have the B and H antigen present. A person with AB blood type will have A, B, and H antigens present. And finally, a person with O blood type will only have the H antigen present. This means all blood types have the H antigen, which explains why the O blood type is known as the "universal donor".

Cell Adhesion:

Many cells produce specific carbohydrate-binding ligands, known as lectins, which mediate cell-adhesion with oligosaccharides. Selectins - a family of lectins - mediate certain cell-cell adhesion processes, including those of leukocytes to endothelial cells. In an immune response, endothelial cells can express certain selectins transiently in response to damage or injury to the cells. In response, a reciprocal selectin-oligosaccharide interaction will occur between the two molecules which allow the white blood cell to help eliminate the infection or damage. Protein-Carbohydrate bonding is often mediated by hydrogen bonding and van der Waals forces.