Carbohydrates can be attached to proteins to form glycoproteins. In glycoproteins, the carbohydrate chains are either attached to the nitrogen atom in the side chain of asparagine (N-linkage) or to the oxygen in the side chain or serine or threonine (O-linkage.) There is also a third category of glycoproteins, non enzymatic glycosylated glycoproteins.
In N-linked glycoproteins, an asparagine is only available for glycosylation if the residue is part of an Asn-X-Ser or Asn-X-Thr sequence (where X can be any residue.) While not all possible glycosylation sites are glycosylated, this specificity allows potential glycosylation sites to be detected.
Furthermore, all N-linked glycoproteins begin as an oligosaccharide attached to a specialized lipid molecule, dolichol phosphate, which resides in the ER membrane. As the oligosaccharide is transferred to the selected aparagine receptor, the structure is "flipped" through the ER membrane where additional sugars are then added by enzymes in the ER lumen. These N-linked glycoproteins are then transported to the Golgi complex where the carbohydrates can be modified to their final configurations.
Unlike the N-linked glycoproteins which arrive in the Golgi as a glycoprotein, O-linked glycoproteins have their sugar components developed solely within the Golgi complex. In the Golgi, the addition of a carbohydrate to the serine and threonine residue of a protein results in an O-linked glycoprotein.
Non-enzymatic glycosylated glycoproteins: synthesized by chemically adding sugar to the polypeptides.
Glycoproteins can be found throughout matrices and act as receptors on cell surfaces that can then bring other cells and proteins (for example, collagen) together giving strength and support for a strong matrix system. For example, Proteoglycan-linking glycoproteins can cross link other proteoglycan molecules and create a formation of a ordered structure within the cartilage tissue. In nerve tissue, glycoproteins are also very abundant in the gray matter portion of the brean and appear to be associated with synaptosomes, axons, and other microsomes. Glycoproteins also play a huge role in the blood clotting mechanism because of their varying identities and roles as prothrombin, thrombin and fibrinogen. In addition, select bacteria contain a mucous like layer that surrounds the outermost components of their constituent cell walls which are also made of glycoproteins composed of very high molecular weight. These glycoproteins are commonly known as cellulose, also found in the structure of plants. The composition of such glycoproteins is important to the plant cell because the rigidity and the homogeneous form of such glycoproteins is what allows plants to stand upright. The flagella of bacteria are also made of structural glycoproteins in the sense that they are in bundles protruding from the cells surface, used to rotate and propel the cell in a specific direction.
Mucins are high molecular weight glycoproteins which can often be found protecting internal epithelial surfaces such as the respiratory, digestive, and urinary tracts of humans. Additionally, sweat glands also often secrete glycoproteins which can protect the skin.
Glycoproteins are important in the binding of a sperm cell to the surface of the egg during reproduction.
HCG (Human chorionic gonadotropin) and EPO (erythropoietin) are both glycosylated proteins that function as hormones in the human body.
Due to the variety of glycoproteins, one being N linked while the O linked (pertaining to the amine terminus of Asn or the carboxyl terminus in Ser or Thr) both have different roles on oligosaccharide chains on the structure-function of glycoprotein hormones. In order for the differentiation of roles to be discovered on a hormonal level, an experiment was conducted in a fashion that O-glycosylation on the structure function of glycoprotein hormones were isolated and expressed in a CHO mutant cell line, 1dID, which specifically had a reversible defect in the protein o-glycosylation with only N-linked oligosaccharides being functional. The same was done for the N-glycosylation on the structure function of glycoprotein hormones excepted it was isolated into a different CHO mutant cell line which specifically had a reversible defect in the protein n-glycosylation with only o-linked oligosaccharides being functional. The results then indicated that the O-linked oligosaccharides played a very minor role in the receptor binding and signal transduction of the glycoprotein hormones dictated by the fact that the activity of the hormones remained unchanged. However the o-linked oligosaccharides did express a critical necessity for in vivo half-life and bioactivity. In other words, every other function that o-linked oligosaccharides previously had besides the assumed association with hormones was affected due to the absence of the glycoprotein. When N-linked oligosaccharide absence was analyzed, it was found that there was a development of glycoprotein hormone antagonists. In the specific case of hTS, the development of such antagonists can possibly offer therapeutic strategies in the treatment of thyrotoxicosis casued by Graves’ disease and TSH secreting pituitary adenoma.
The specificity of different antibodies is determined by the carbohydrate structure in the glycoprotein. Additionally, both B and T cells contain surface glycoproteins which can bind certain antigens.
- Berg, Tymoczko, and Stryer (2002). Biochemistry. W.H. Freeeman and Company: New York. 5th edition: pg. 306-309.
- Ivatt, Raymond J. (1984) The Biology of Glycoproteins. Plenum Press: New York.
- Gottschalk, Alfred (1972 Glycoproteins: Their Composition, Structure, and Function. Elsevier Publishing Company: New York.
Fuad Fares, The role of O-linked and N-linked oligosaccharides on the structure–function of glycoprotein hormones: Development of agonists and antagonists, Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1760, Issue 4, April 2006, Pages 560-567, ISSN 0304-4165, 10.1016/j.bbagen.2005.12.022.