Structural Biochemistry/Proteins/Protein Glycosylation

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Glycoproteins[edit | edit source]

Glycoprotein or Oligosaccharide attached protein

After post-translation, proteins can be further modified by being attached to carbohydrate groups (sugars) by glycosidic bonds via the process called "glycosylation", and the newly formed molecule is called a "glycoprotein". There are two types of glycosidic bonds that can occur in this process, called N-linkage and O-linkage.

N-linkage: The nitrogen atom in the side chain of Asparagine is attached to the sugar. The sequence can be Asn-X-Ser or Asn-X-Thr, where X is any kind of amino acid except proline.

O-linkage: The oxygen atom in the side chain of serine or threonine amino acids is attached to the sugar.

Proteins are often glycosylated while secretion from a cell. The glycosylated proteins are mostly found in the blood serum. Being one of the components in the cell membrane, they are responsible for combining cells or even combining sperm and eggs.

N-linked glycosidic bond.png
O-linked glycosidic bond.png

Protein Glycosylation[edit | edit source]

Protein glycosylation is an enzyme-directed chemical reaction that takes place in the ER(Endoplasmic Reticulum) and in the Golgi Apparatus body of the cell.[1] General glycosylation within the ER helps with folding, and glycosylation in the Golgi body tells a protein where to go. The ribosomes sticking on the cytoplasmic surface of the ER membrane synthesize the protein. The peptide chain is then sent into the lumen of the ER. There are N-linked and O-linked glycosylation processes. This is determined by whether the sugars in glycoproteins are attached to the amide nitrogen on the amino acid asparagine, or to the oxygen on the side chains of either serine or threonine. The N-linkage glycosylations happens in both ER and in the Golgi complex while the O-linked glycosylation only occurs in the Golgi complex. In the Golgi complex, the glycosylated proteins derive the carbohydrates out, which change their shape to keep working in the Golgi complex. Proteins derived from the glycoproteins diffuse into vesicles and are transported into different places according to the signals instructed by the amino acid sequence and the three-dimensional structures.

N-linked glycosylation mostly takes place in eukaryotes and archaea, but rarely in bacteria. When a 14-sugar chain, including 2 N-acetylglucosamine molecules, 3 glucose, and 9 mannose, is attached to the asparagine amino acid in the target protein, dolichol molecle is carried by reaction and sent into the ER lumen. There are two kinds of N-linked oligosaccarides: High-mannose oligosaccharides, and complex oligosaccharides. High-mannose oligosaccharides is a combination of the 2 N-acetylglucosamine molecules and many numbers of mannose residues attached. This is the most common chain. The complex oligosaccharides is the combination of any number and of any kinds of saccharides attaching together. The modification of both two types depends on the accessibility of the modified proteins in the Golgi complex. If the oligosaccharides are not accessible, then the high-mannose will not be cleaved for further modification.

The cytoplasm is not a place for protein glycosylation, because sugars and complex enzymes are stored in the lumenal side of the ER, so the proteins are not glycosylated as they are above.

Significance of Protein Glycosylation[edit | edit source]

Glycosylation can avoid the incorrect folding of the original proteins. Many proteins do not fold correctly unless they undergo glycosylation. It also increases the stability of the protein structures in blood so that they will not degrade as quickly as those unglycosylated proteins. For example, glycoproteins linked at the amide nitrogen in asparagine in the protein have increased stability. N-linked glycosylation of this sort occurs when the protein sequence Asn-X-Thr or Asn-X-Ser is reached. X, in this case can be any amino acid except for proline. Glycosylation helps to adhere between cells. This mechanism of cell to cell adhesion is especially vital in cells of the immune system. [2]

Disease Caused by Incorrect Glycosylation[edit | edit source]

Congenital disorders of Glycosylation is a type of disease caused by incorrect glycosylation. I-cell disease is an example of such congenital disorders. The lysosomes include undigested glycosaminoglycans and glycolipids because the responsible enzymes containing a mannose residue are missed to degrade them. In other words, the mannose residues are not being modified in the enzymes so that they cannot degrade the glycosaminoglycan and glycolipids. Urine and blood also contain high level of such enzymes. Because of this mistake, the carbohydrates and the glycosaminoglycans will accumulate more and more and finally cause patients in a pathological condition.

Glycosylation Influences on Protein Folding[edit | edit source]

Glycosylation is a posttranslational modification to proteins which influences the tertiary structure based on the placement of glycols on the protein and the timing in the folding process when the glycols get introduced. "The magnitude of thermodynamic protein stabilization by glycosylation depends on the properties of both the carbohydrate and the protein moieties."[3] Glycosylation stabilization is dependent on the position of the glycol in the protein. Also, it is shown that the size of the oligosaccharide is not as important of a factor on the outcome in the protein structure as the properties of the oligosaccharide attached to the protein. In highly structured regions of proteins glycolysation destabilizes the section and in highly flexible regions the glycol stabilizes the region. Furthermore the glycols either keep areas expanded if they are added before protein folding commences or compact the size of the overall protein if added at a later time in the protein folding sequence. Glycolysation often results in reduced flexibility of the folded protein. The stabilization conferred by glycolysation is similar to that of molecular crowding and confinement yet has little influence on the folding transition temperature when compared to these other effects. However, it is hypothesized that the stabilization by glycolysation increases in crowded molecular environments, but this has yet to be tested. [4]

Erythropoietin (EPO)[edit | edit source]

An example of a glycoprotein that has provided much effect in the medical field is Erythropoietin also known as EPO. This glycoprotein has improved the treatment for anemia particularly induced by cancer chemotherapy. It is secreted by the kidneys and stimulates the production of red blood cells. EPO is made of 165 amino acid. It is N-glycoslyated at the asparagine residue and O-glycosylated on a serine residue. It is 40% carbohydrate by weight. The glycoslyation enhances stability of the protein in the blood as compared to the unglycoslyated protein which only carries about 10% of the bioactivity. This is because protein is rapidly removed from the blood by the kidney. Although recombinant human EPO has aided the treatment of anemia it has also been misused by athletes to increase their red blood cell count and their oxygen carrying capacity. However modern drug testing can usually distinguish between this and natural EPO.

References[edit | edit source]

^ "glycosylation." . WikiAnswer. 18 Nov. 2008 <>.

^ Berg, Jeremy M. BIOCHEMISTRY. Vol. 11. 5th ed. W. H. FREEMAN AND COMPANY, 2002. 18 Nov. 2008 <>.

^ Shental-Bechor, Dalit, and Yaakov Levy. "Folding of Glycoproteins: toward Understanding the Biophysics of the Glycosylation Code." Current Opinion in Structural Biology 19.5 (2009): 524-33. ScienceDirect. ScienceDirect hosted at, 3 Aug. 2009. Web. 18 Nov. 2010. <>.