Structural Characteristics and Functions of Glycoproteins, Proteoglycans and Glycolipids

Sugar is an important nutrient for the human body, and its primary physiological function is to provide energy and carbon sources for life activities. In addition, sugar also participates in the composition of glycoproteins and glycolipids, and regulates cell information transmission. Monosaccharides are polymerized by glycosidic bonds to form oligosaccharides or polysaccharides, also called glycans. Glycans are covalently linked with proteins or lipids to form complex biological macromolecules, which are divided into glycoproteins, proteoglycans and glycolipids, also known as sugar complexes.

Figure 1 Schematic Representation of Glycosylation Diversity (Costa et al., 2020).

Glycoprotein is formed by carbohydrate molecules that covalently bond with protein molecules. There are 7 kinds of monosaccharides that make up glycans in the glycoprotein molecules: glucose, galactose, mannose, N-acetylgalactosamine, N-acetylglucosamine, fucose, and N-acetylneuraminic acid.

According to the different ways of connection with proteins, glycoproteins can be categorized as N-linked glycans and O-linked glycans. N-linked glycans are linked to the amide nitrogen of asparagine residues in protein molecules. O-linked glycans are connected to the serine or threonine hydroxyl groups in protein molecules. The synthesis of N-linked glycan uses long terpene alcohol as a glycan carrier, while O-linked glycan synthesis does not require a glycan carrier. Statistically, about one-third of the proteins in human cells are glycoproteins and perform different functions. Glycans in glycoprotein molecules can affect the conformation, polymerization, dissolution and degradation of the protein part and participate in the mutual recognition and binding of glycoproteins.

Proteoglycans are dominated by glycan content, and glycosaminoglycans are covalently linked to different core proteins to form sugar complexes. Glycosaminoglycans are heteropolysaccharides formed by the repeated connection of disaccharide units without branching. One of the disaccharide units is glycosamine (N-acetylglucosamine or N-acetylgalactosamine) and the other is uronic acid (glucuronic acid or iduronic acid). There are six essential glycosaminoglycans in the body: chondroitin sulfate, dermatan sulfate, keratan sulfate, hyaluronic acid, heparin, and heparan sulfate. These glycosaminoglycans are composed of repeating disaccharide units. Except for hyaluronic acid, all other glycosaminoglycans contain sulfuric acid. Moreover, the protein that is covalently bound to the glycosaminoglycan chain is called the core protein. Core proteins contain corresponding glycosaminoglycan substitution domains, and some proteoglycans are anchored to the cell surface or extracellular matrix macromolecules through unique domains of the core protein. The primary function of proteoglycan is to form the intercellular matrix, which can bind to the hyaluronic acid receptor on the cell surface and affect cell-to-cell adhesion, migration, proliferation and differentiation.

Glycolipid

Glycolipids are complex lipids that carry one or more covalently linked sugar groups. Due to the difference in lipids, glycolipids can be divided into sphingomyelin, glyceroglycolipid and steroid-derived glycolipid. Like sphingomyelin, glycosphingolipids are compounds based on ceramide. The ceramide 1-hydroxyl group in the sphingomyelin molecule is aminated by phosphatidylcholine or phosphatidylethanol, while ceramide 1-hydroxyl group in the glycosphingolipid molecule is glycosylated to form a glycoside compound. Furthermore, the monosaccharides in glycosphingolipid molecules are mainly composed of D-glucose, D-galactose, N-acetylglucosamine, N-acetylgalactosamine, fucose and sialic acid. Glycosphingolipids can be divided into neutral glycosphingolipids and acidic glycosphingolipids according to whether the molecule contains sialic acid or sulfate-based components. For example, cerebrosides are neutral glycosphingolipids without the sialic acid, and gangliosides are acid glycosphingolipids containing sialic acid.

Glycans are involved in cell recognition, cell adhesion, cell differentiation, immune recognition, signal transduction, microbial pathogenic processes and tumor metastasis processes. Creative Proteomics reserved extensive experience in glycomics research, and can provide customized glycan analysis services for customers in many regions and countries.

Reference

Costa, A. F., Campos, D., Reis, C. A., & Gomes, C. (2020). Targeting glycosylation: a new road for cancer drug discovery. Trends in cancer, 6(9), 757-766.

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