PROTEOGLYCANS: STRUCTURE, CHARACTERISTICS, FUNCTION, EXAMPLES - BIOLOGY - 2025

The proteoglycans are glycosylated proteins, generally associated with glycosaminoglycan substituents (GAGs) anionic. They are usually found on the outside of the cell membrane or "fill" the extracellular space, so they are part of many connective tissues.

Of these complex macromolecules, the most studied and analyzed have been those of cartilaginous cells in vertebrate animals, since the extracellular matrix in these comprises more than 90% of the dry weight of the tissue they compose, where they influence, among other things, resistance to compression.

Structure of the extracellular matrix that makes up hyaline cartilage (Source: See page for author / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) via Wikimedia Commons)

Structurally, proteoglycans contribute to the organization of the extracellular matrix, which gives many individual tissues or cells their most distinctive physical properties. Furthermore, these are important for many intercellular communication and signaling events.

They are extremely abundant, ubiquitous (they are in numerous types of cells) and complex proteins, whose biological functions and biochemical properties derive fundamentally from the characteristics of their carbohydrate components, which have a high hydration capacity.

They actively participate in intercellular communication, in adhesion and migration processes and have also been implicated in the development of various tissues in animals, such as the perineuronal networks of the nervous system.

Structure and characteristics of proteoglycans

Proteoglycans are glycosylated proteins on the extracellular surface, although there are some that can be found in intracellular compartments. They are generally very abundant molecules, but their abundance depends on the type of cell considered.

Ordinarily, the carbohydrate portion of a proteoglycan consists of glycosaminoglycan molecules, which are linear polysaccharides composed of repeating disaccharides, usually of an acetylated amino sugar that alternates with uronic acid.

Its general structure, therefore, consists of a protein "core" that can associate with more than 100 unbranched glycosaminoglycan chains, linked by means of O-glycosylation.

They are quite diverse molecules in terms of structure, shape and function. In the cells of vertebrate animals, for example, several combinations of different types of proteins and different classes of glycosaminoglycans have been identified, namely:

Protein

- Cell surface transmembrane proteins (extracellular matrix)

- Proteins covalently linked to glycosylphosphatidylinositol (GPI) anchors)

Glucosaminoglycans

- Hyaluronan (HA)

- Chondroitin sulfate (CS)

- Keratan sulfate (KS)

- Dermatan sulfate (DS)

- Heparan sulfate (HS)

Scheme of proteoglycans and some combinations of glycosaminoglycans (Source: Mfigueiredo / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) via Wikimedia Commons)

Some proteoglycans such as syndecans, which are transmembrane proteins, are attached to 2 chains of heparan sulfate and 1 of chondroitin sulfate; Meanwhile, another proteoglycan, aggrecan (cartilage specific) has about 100 chains of chondroitin sulfate and 30 of keratan sulfate.

From the foregoing it is understood that the glycosylation characteristics of each protein, as well as the type of cell to which it belongs, are those that define the identity of each proteoglycan on the cell surface.

Function

Their functions depend on the structural characteristics of proteoglycans. This is particularly true for those characteristics that are related to the glycosaminoglycan portion, since these molecules are what allow the protein to interact with other elements on the cell surface.

Those proteins rich in heparan sulfate residues can bind with relative ease to different growth factors, to other components of the extracellular matrix, to enzymes, protease inhibitors, chemokines, etc., therefore they play a fundamental role in the transduction of signals to the intracellular environment.

Thus, proteoglycans can fulfill structural functions in the matrix or they can have more specific functions in the transmission of messages from the extracellular environment to the cytosolic space.

In recent years, interest in the study of proteoglycans has grown considerably, a fact that is related to the discovery of the importance that these molecules have in some pathological conditions in human beings.

An example of these is the Simpson-Golabi-Behmel syndrome (GBSS), characterized by exaggerated pre- and post-natal growth, birth defects, and susceptibility to tumor formation associated with mutations in a proteoglycan rich in heparan sulfate. and anchored by GPI.

Main proteoglycans of the arteries and blood vessels. The molecular weight of the protein core is shown (Source: ALEISF / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0) via Wikimedia Commons)

Cell functions

Virtually all cellular processes that involve molecular interactions on the cell surface, such as cell-matrix, cell-cell and ligand-receptor interactions have to do, in one way or another, with proteoglycans, since they are capable of binding to large amounts of other molecules and are considerably abundant on the surface.

During the development of the nervous system and also during the invasion of a tumor and metastasis, that is, events that have to do with movements and cell extensions or extensions, proteoglycans exert very active functions.

These glycosylated proteins also participate in the processes of adhesion, proliferation and establishment of cell shape, and those that are transmembrane proteins that possess a cytosolic domain participate in transduction and signaling cascades.

Examples of proteoglycans

Aggrecano

Aggrecan is the main proteoglycan present in cartilaginous tissue, which is associated with fragments of the glycosaminoglycan "hyaluronan" (HA) in the extracellular matrix of chondrocytes.

Hyaluronan is a linear glycosaminoglycan composed of alternating residues of glucuronic acid and N-acetylglucosamine, which can be found both on the cell surface and in the extracellular matrix and inside cells.

The binding of hyaluronan to aggrecan occurs through a "binding protein" that forms important aggregates with molecular weights of up to several million daltons.

Many age-related joint diseases are associated with increased aggrecan and hyaluronan aggregation.

Pelecano

In the renal glomeruli, the basement membrane is mainly made up of a proteoglycan known as pelecan, which is associated with portions of heparan sulfate. This proteoglycan has important functions as an anionic charge selectivity site during glomerular filtration.

This proteoglycan has the largest protein core that has been observed in any of these molecules and it is speculated that this protein domain may interact with other macromolecules present in the basement membrane.

Decorin

Decorin is a small interstitial proteoglycan and is characterized by having a single glycosaminoglycan chain and a small protein nucleus. It is an important component of many connective tissues, it binds to type I collagen fibers and participates in the assembly of the extracellular matrix.

References

1. Godfrey, M. (2002). Extracellular matrix. In Asthma and COPD (pp. 211-218). Academic Press.
2. Iozzo, RV, & Schaefer, L. (2015). Proteoglycan form and function: a comprehensive nomenclature of proteoglycans. Matrix Biology, 42, 11-55.
3. Muncie, JM, & Weaver, VM (2018). The physical and biochemical properties of the extracellular matrix regulate cell fate. In Current topics in developmental biology (Vol. 130, pp. 1-37). Academic Press.
4. Perrimon, N., & Bernfield, M. (2001, April). Cellular functions of proteoglycans-an overview. In Seminars in cell & developmental biology (Vol. 12, No. 2, pp. 65-67). Academic Press.
5. Petty, RE, & Cassidy, JT (2011). Structure and function. In Textbook of pediatric rheumatology (pp. 6-15). WB Saunders.
6. Yanagishita, M. (1993). Function of proteoglycans in the extracellular matrix. Pathology International, 43 (6), 283-293.