Proteoglycan


Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan chain. The point of attachment is a serine residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge. The Ser residue is generally in the sequence -Ser-Gly-X-Gly-, although not every protein with this sequence has an attached glycosaminoglycan. The chains are long, linear carbohydrate polymers that are negatively charged under physiological conditions due to the occurrence of sulfate and uronic acid groups. Proteoglycans occur in connective tissue.

Types

Proteoglycans are categorized by their relative size and the nature of their glycosaminoglycan chains.
Types include:
GlycosaminoglycansSmall proteoglycansLarge proteoglycans
chondroitin sulfate/dermatan sulfatedecorin, 36 kDa
biglycan, 38 kDa		versican, 260–370 kDa, present in many adult tissues including blood vessels and skin
heparan /chondroitin sulfatetestican, 44 kDaperlecan, 400–470 kDa
chondroitin sulfatebikunin, 25 kDaneurocan, 136 kDa
aggrecan, 220 kDa, the major proteoglycan in cartilage
brevican, 145kDa
keratan sulfatefibromodulin, 42 kDa
lumican, 38 kDa

Certain members are considered members of the "small leucine-rich proteoglycan family". These include decorin, biglycan, fibromodulin and lumican.

Function

Proteoglycans are a major component of the animal extracellular matrix, the "filler" substance existing between cells in an organism. Here they form large complexes, both to other proteoglycans, to hyaluronan, and to fibrous matrix proteins, such as collagen. The combination of proteoglycans and collagen form cartilage, a sturdy tissue that is usually heavily hydrated. They are also involved in binding cations and water, and also regulating the movement of molecules through the matrix. Evidence also shows they can affect the activity and stability of proteins and signalling molecules within the matrix. Individual functions of proteoglycans can be attributed to either the protein core or the attached GAG chain. They can also serve as lubricants, by creating a hydrating gel that helps withstand high pressure.

Synthesis

The protein component of proteoglycans is synthesized by ribosomes and translocated into the lumen of the rough endoplasmic reticulum. Glycosylation of the proteoglycan occurs in the Golgi apparatus in multiple enzymatic steps. First, a special link tetrasaccharide is attached to a serine side chain on the core protein to serve as a primer for polysaccharide growth. Then sugars are added one at a time by glycosyl transferase. The completed proteoglycan is then exported in secretory vesicles to the extracellular matrix of the tissue.

Clinical significance

An inability to break down proteoglycans is characteristic of a group of genetic disorders, called mucopolysaccharidoses. The inactivity of specific lysosomal enzymes that normally degrade glycosaminoglycans leads to the accumulation of proteoglycans within cells. This leads to a variety of disease symptoms, depending upon the type of proteoglycan that is not degraded. Mutations in the gene encoding the galactosyltransferase B4GALT7 result in a reduced substitution of the proteoglycans decorin and biglycan with glycosaminoglycan chains, and cause a spondylodysplastic form of Ehlers-Danlos syndrome.