What Glycoproteins Are and What They Do

A glycoprotein is a type of protein molecule that has had a carbohydrate attached to it. The process either occurs during protein translation or as a posttranslational modification in a process called glycosylation.

The carbohydrate is an oligosaccharide chain (glycan) that is covalently bonded to the polypeptide side chains of the protein. Because of the -OH groups of sugars, glycoproteins are more hydrophilic than simple proteins. This means glycoproteins are more attracted to water than ordinary proteins. The hydrophilic nature of the molecule also leads to the characteristic folding of the protein's tertiary structure.

The carbohydrate is a short molecule, often branched, and may consist of:

• simple sugars (e.g., glucose, galactose, mannose, xylose)
• amino sugars (sugars that have an amino group, such as N-acetylglucosamine or N-acetylgalactosamine)
• acidic sugars (sugars that have a carboxyl group, such as sialic acid or N-acetylneuraminic acid)

O-Linked and N-Linked Glycoproteins

Glycoproteins are categorized according to the attachment site of the carbohydrate to an amino acid in the protein.

• O-linked glycoproteins are ones in which the carbohydrate bonds to the oxygen atom (O) of the hydroxyl group (-OH) of the R group of either the amino acid threonine or serine. O-linked carbohydrates may also bond to hydroxylysine or hydroxyproline. The process is termed O-glycosylation. O-linked glycoproteins are bound to sugar within the Golgi complex.
• N-linked glycoproteins have a carbohydrate bonded to the nitrogen (N) of the amino group (-NH₂) of the R group of the amino acid asparagine. The R group is usually the amide side chain of asparagine. The bonding process is called N-glycosylation. N-linked glycoproteins gain their sugar from the endoplasmic reticulum membrane and then are transported to the Golgi complex for modification.

While O-linked and N-linked glycoproteins are the most common forms, other connections are also possible:

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• P-glycosylation occurs when the sugar attaches to the phosphorus of phosphoserine.
• C-glycosylation is when the sugar attaches to the carbon atom of an amino acid. An example is when the sugar mannose bonds to the carbon in tryptophan.
• Glypiation is when a glycophosphatidylinositol (GPI) glycolipid attaches to the carbon terminus of a polypeptide.

Glycoprotein Examples and Functions

Glycoproteins function in the structure, reproduction, immune system, hormones, and protection of cells and organisms.

Glycoproteins are found on the surface of the lipid bilayer of cell membranes. Their hydrophilic nature allows them to function in the aqueous environment, where they act in cell-cell recognition and binding of other molecules. Cell surface glycoproteins are also important for cross-linking cells and proteins (e.g., collagen) to add strength and stability to a tissue. Glycoproteins in plant cells are what allows plants to stand upright against the force of gravity.

Glycosylated proteins are not just critical for intercellular communication. They also help organ systems communicate with each other. Glycoproteins are found in brain gray matter, where they work together with axons and synaptosomes.

Hormones may be glycoproteins. Examples include human chorionic gonadotropin (HCG) and erythropoietin (EPO).

Blood clotting depends on the glycoproteins prothrombin, thrombin, and fibrinogen.

Cell markers may be glycoproteins. The MN blood groups are due to two polymorphic forms of the glycoprotein glycophorin A. The two forms differ only by two amino acid residues, yet that is enough to cause problems for persons receiving an organ donated by someone with a different blood group. The Major Histocompatibility Complex (MHC) and H antigen of the ABO blood group are distinguished by glycosylated proteins.

Glycophorin A is also important because it's the attachment site for Plasmodium falciparum, a human blood parasite.

Glycoproteins are important for reproduction because they allow for the binding of the sperm cell to the surface of the egg.

Mucins are glycoproteins found in mucus. The molecules protect sensitive epithelial surfaces, including the respiratory, urinary, digestive, and reproductive tracts.

The immune response relies on glycoproteins. The carbohydrate of antibodies (which are glycoproteins) determines the specific antigen it can bind. B cells and T cells have surface glycoproteins which bind antigens, as well.

Glycosylation Versus Glycation

Glycoproteins get their sugar from an enzymatic process that forms a molecule that would not function otherwise. Another process, called glycation, covalently bonds sugars to proteins and lipids. Glycation is not an enzymatic process. Often, glycation reduces or negates the function of the affected molecule. Glycation naturally occurs during aging and is accelerated in diabetic patients with high glucose levels in their blood.

Sources

• Berg, Jeremy M., et al. Biochemistry. 5th ed., W.H. Freeman and Company, 2002, pp. 306-309.
• Ivatt, Raymond J. The Biology of Glycoproteins. Plenum Press, 1984.