GLYCOPROTEINS: STRUCTURE, FUNCTIONS, CLASSES AND EXAMPLES - BIOLOGY - 2024

The glycoproteins or glycoproteins are transmembrane proteins that are part of the great family of membrane glycoconjugates and are present in animals, plants and microorganisms such as bacteria, yeast, and Archaea.

They were defined for the first time in 1908 by the Protein Nomenclature Committee of the American Society of Biochemists and are the result of the glycosidic union of a protein with a carbohydrate portion called glucan.

Structure of the Lectin monomer of a legume (Source: User: Tomixdf via Wikimedia Commons)

They are proteins that are particularly abundant on the surface of the plasma membrane of many cells and constitute an important part of the carbohydrate layer that covers them, which in many cases is called the glycocalyx.

The precursor proteins of the glycoproteins are covalently modified in the endoplasmic reticulum and the Golgi complex of many eukaryotes after their translation, although there are also cases of glycosylation in the cytosol, but they are less common and occur with only one type of sugar.

Protein glycosylation often has important functional effects on its activity, since it can participate in folding and, therefore, in the establishment of its tertiary structure.

Glycans have multiple biologically important functions for the cell, since they can confer specificity to cells and participate in intracellular and intercellular signaling processes, since they are ligands for endogenous and exogenous receptors.

Glycoproteins, as well as the rest of the glycoconjugates, are so important that a cell dedicates up to 1% of its genome to the glycosylation machinery and, in humans, more than 70% of proteins are modified by glycosylation.

Structure

The structure of glycoproteins is studied based on their amino acid sequence, the glycosylation sites within the sequence, and the structures of the glycan portions that bind at those sites.

The oligosaccharide chains that are linked by glycosylation to these proteins are generally very diverse, but they are short, since they do not exceed 15 sugar residues. Some proteins have a single oligosaccharide chain, but others may have more than one and these may be branched.

The union between oligosaccharides and proteins occurs through the anomeric carbon of the carbohydrate and the hydroxyl group (-OH) of a serine or threonine residue, in the case of O -glycosylation, or through the amide nitrogen of an asparagine residue, in the case of N-glycosylation.

The carbohydrates thus bound can represent up to 70% of the molecular weight of a glycoprotein and the characteristics of the carbohydrate portion (size and charge, for example) can protect some proteins against enzymatic proteolysis.

The same protein can have, in different tissues, different glycosylation patterns that make it a different glycoprotein, since the complete structure includes not only the amino acid residues and their spatial arrangements, but also the oligosaccharides attached to them.

Among the sugar residues that are repeatedly found in glycoproteins are: D-galactose, D-mannose, D-glucose, L-fucose, D-xylose, L-arabinofuranose, N-acetyl-D-glucosamine, N-acetyl -D-galactosamine, some sialic acids and modifications of all these.

Features

Structural

From a structural point of view, glycoproteins provide carbohydrate chains that participate in the protection and lubrication of cells, since they are capable of hydrating and forming a viscous substance that resists mechanical and chemical aggressions.

Some glycoproteins are also found in bacteria and archaea, and these are important components of the S layer, which is the outermost layer of the cell envelope.

In addition, they are also found as constituents of flagellin proteins, which are part of the flagellar filaments used as locomotor organs.

Plants also possess structural glycoproteins that are characterized by complex glycosylation patterns and that can be found as part of the cell wall structure or in the extracellular matrix.

Cell recognition

Glycoproteins have important functions as inter-cell recognition sites, since many receptors on the cell surface are capable of recognizing specific oligosaccharide sequences.

An example of the intercellular recognitions that occur by means of the oligosaccharide chains on the cell surface is the case of the recognition between the ovule and the sperm, necessary for the phenomenon of fertilization to occur in multicellular organisms with sexual reproduction.

Blood groups in humans are determined by the identity of the sugars attached to the glycoproteins that specify them. Antibodies and many hormones are also glycoproteins and their functions are essential for the body's signaling and defense.

Cell adhesion

The T cells of the mammalian immune system possess a glycoprotein with adhesion domains known as CD2, which is a key component for immune stimulation since it mediates the binding between the lymphocyte and antigen-presenting cells through its receptor, the CD58 glycoprotein.

Some viruses that have important pathogenic functions for many mammals, including humans, possess surface glycoproteins that function in the adhesion processes of the viral particle to the cells they parasitize.

Such is the case of the GP120 protein of the Human Acquired Immunodeficiency Virus or HIV, which interacts with a surface protein of human cells known as GP41 and which collaborates with the entry of the virus into the cell.

In the same way, many glycosylated proteins participate in important cell adhesion processes that take place in the ordinary life of cells present in many tissues of multicellular organisms.

Glycoproteins as therapeutic targets

These protein-carbohydrate complexes are the preferred targets for many pathogens such as parasites and viruses, and many glycoproteins with aberrant glycosylation patterns have critical roles in autoimmune diseases and cancers.

For these reasons, various researchers have taken on the task of proposing these proteins as possible therapeutic targets and for the design of diagnostic methods, new generation therapies, and even for the design of vaccines.

Lessons

The classification of glycoproteins is based primarily on the nature of the glycosidic bond that joins the protein and carbohydrate moieties and on the characteristics of the attached glycans.

According to the sugar residues, glycoproteins with monosaccharides, disaccharides, oligosaccharides, polysaccharides and derivatives of these can be had. Some authors consider a classification of glycoproteins in:

- Proteoglycans, which are a subclass within the group of glycoproteins that contains, in the carbohydrate portion, polysaccharides composed mainly of amino sugars (glycosaminoglycans).

- Glycopeptides, which are molecules composed of carbohydrates linked to oligopeptides formed by amino acids in their L and / or D conformations.

- Glyco amino acids, which are amino acids linked to a saccharide through any type of covalent bond.

- Glycosyl amino acids, which are amino acids linked to a saccharide portion through O-, N-, or S-glycosidic bonds.

In the nomenclature of these proteins thus linked to carbohydrates, the prefixes O-, N- and S- are used to specify through which bonds the sugars are attached to the polypeptide chain.

Examples

- Glycophorin A is one of the best-studied glycoproteins: it is an integral protein of the membrane of erythrocytes (cells or red blood cells) and has 15 chains of oligosaccharides covalently linked to amino acid residues of the N-terminal region a through O-glycosidic bonds and a chain linked by an N-glycosidic bond.

- Most of the proteins in the blood are glycoproteins and this group includes immunoglobulins and many hormones.

- Lactalbumin, a protein present in milk is glycosylated, as well as many pancreatic and lysosomal proteins.

- Lectins are carbohydrate-binding proteins and therefore have multiple functions in recognition.

- It is also necessary to highlight many animal hormones that are glycoproteins; Among these, mention can be made of lutropin (LH), follitropin (FSH) and thyrotropin (TSH), which are synthesized in the anterior pituitary gland, and chorionic gonadotropin that is produced in the placenta of humans, primates and equines.

These hormones have reproductive functions as LH stimulates steroidogenesis in the ovaries and testicular Leydig cells.

- Collagen, an abundant protein present primarily in the connective tissues of animals, represents a huge family of glycoproteins made up of more than 15 types of proteins that, although they have many characteristics in common, are quite different.

These proteins contain "non-collagenic" portions, some of which are made up of carbohydrates.

- Extensins are plant proteins that consist of a network of insoluble glycoproteins that are rich in hydroxyproline and serine residues. They are found in the wall of plant cells and are thought to act as a defense against different types of stress and pathogens.

- Plants also have lectin-like proteins and a special example of these are potato lectins, which apparently have the ability to agglutinate blood cells such as erythrocytes.

- Last, but not least, mucins can be named, which are glycoproteins secreted in the mucosa and are part of saliva in animals, mainly fulfilling lubrication and signaling functions.

References

1. Montreuil, J., Vliegenthart, J., & Schachter, H. (1995). Glycoproteins. (A. Neuberger & L. Deenen, Eds.). Elsevier.
2. Nelson, DL, & Cox, MM (2009). Lehninger Principles of Biochemistry. Omega Editions (5th ed.).
3. Struwe, W., & Cosgrave, E. (2011). Functional and Structural Proteomics of Glycoproteins. (R. Owens & J. Nettleship, Eds.). London: Springer.
4. Voet, D., & Voet, J. (2006). Biochemistry (3rd ed.). Editorial Médica Panamericana.
5. Wittman, V. (2007). Glycopeptides and Glycoproteins. Synthesis, Structure, and Application. (V. Balzani, J.-M. Lehn, A. de Meijere, S. Ley, K. Houk, S. Schreiber, J. Thiem, Eds.). Leipzig: Springer Science + Business Media, LLC.