Proteoglycans

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Proteoglycans are an important component of the extracellular matrix in animal tissue, for example in cartilage tissue . They are also localized on the cell surface and in intracellular secretory granules .

Proteoglycans are a class of particularly heavily glycosylated glycoproteins - macromolecules made up of a protein and one or more covalently bound carbohydrate groups . In the case of the proteoglycans, the side chains are glycosaminoglycans (GAG). These are long, linear carbohydrate groups made up of repeating disaccharides .

Carbohydrates make up about 95% of the molar mass of proteoglycans, in contrast to glycoproteins, the protein portion of which outweighs the carbohydrate portion.

function

Proteoglycans are a main component of the animal extracellular matrix , which bring about the stabilization between the cells of an organism. Here they form large complexes, both with other proteoglycans and hyaluronic acid , as well as with fiber proteins such as collagen . They are also involved in binding cations and regulating the movement of molecules through the matrix. There is evidence that they can affect the activity and stability of proteins and signaling molecules within the matrix. The function of the proteoglycan can in part be attributed to the protein core or the attached GAG chain.

Proteoglycans can be used as co-receptors for growth factors such as B. the fibroblast growth factor (FGF) and other hormones act. They can also use protease inhibitors such as antithrombin as "docking stations".

Construction and structure

The polyanionic glycosaminoglycan chains (GAG chains) covalently bound to the central protein filament are characteristic of the very heterogeneous family of proteoglycans. These are made up of unbranched polysaccharide chains that are covalently bound to the central filament via a characteristic connecting tetrasaccharide. The polysaccharide chains consist primarily of repeating disaccharide units from an amino sugar (N-acetylglucosamine and N -acetylgalactosamine) and typically a uronic acid. The glycosaminoglycans are linked to the protein core in the Golgi apparatus. The defined compound tetrasaccharide is attached to serine side chains. The serine side chain acts as a "seed" for the gradual polymerization of the GAG ​​into the periphery.

The central hyaluronic acid has bound up to 100 core proteins, which in turn bind approx. 50 keratan sulfate chains (with up to 250 dissaccharide units) and approx. 100 chondroitin sulfate chains (with up to 1000 disaccharide units).

The binding region consists of the tetrasaccharide sequence:

Glucuronyl-β- (1 → 3) -galactosyl-β- (1 → 3) -galactosyl-β- (1 → 4) -xylosyl-β-1-O- (serine).

The formation of even larger macromolecules is also possible. Thus, hyaluronic acid as a 'tie Kiel several proteoglycans non-covalently in a feathery structure. Hyaluronic acid is also a glycosaminoglycan, but it does not occur in proteoglycans per se; it exists as a free, non-protein-bound polysaccharide.

Like glycosaminoglycans, proteoglycans also form relatively rigid structures with a bulky conformation. Even if their mass fraction in the extracellular matrix is ​​not very large, they have an enormous space requirement. Proteoglycans are very hydrophilic and negatively charged at physiological pH due to deprotonated acid groups. As a result, they bind cations with voluminous layers of water. In this way, the proteoglycans form a gel-like extracellular mass in which fiber proteins are stored. Under pressure, water can only be pressed out of the mass until the charge density of the polymers increases so much that further compression by mutually repelling electrostatic forces is prevented.

They are also often referred to as acid mucopolysaccharides.

Grouping of proteoglycans

Proteoglycans are divided into different groups according to their glycosaminoglycan chains:

A proteoglycan can also carry more than one type of glycosaminoglycan chain; z. B. Aggrecan has KS and CS chains. In addition to the glycosaminoglycan chains, the central filaments also often carry N- or O-glycosidically bound oligosaccharides, as they also occur in other glycoproteins. Due to the size of the central protein filament, the proteoglycans of the ECM are divided into two main groups, the large and small proteoglycans. Because of their common structural domains, the large proteoglycans are divided into hyalectans (e.g. Aggrecan, Neurocan, Brevican, Versican and others), which on the one hand bind hyaluronic acid and on the other hand contain the C-type lectin motif, and into non-hyaluronic acid-binding proteoglycans (e.g. B. Perlecan, Agrin, and others). The small proteoglycans of the EZM include the leucine-rich proteoglycans (e.g. Decorin, Biglycan, Fibromodulin, Lumican and others).

For details of the biological function of the proteoglycans, see the article on the extracellular matrix (ECM).

literature

  • Shirley Ayad, Ray Boot-Handford, Martin J. Humphries, Karl E. Kadler, C. Adrian Shuttleworth: The Extracellular Matrix. FactsBook. 2nd edition. Academic Press, London et al. 1998, ISBN 0-12-068911-1 , p. 14 ff.