Proteoglycans are a special class of glycoproteins that are covalently linked by one or more glycosaminoglycans and a core protein. In addition to glycosaminoglycan chains, proteoglycans have some N- or (and) O-linked oligosaccharide chains. Proteoglycans are not only distributed in the extracellular matrix, but also in the cell surface and secretory granules in the cell.
Figure1. Aggrecan, the major proteoglycan in cartilage, has 2316 amino acids.
Proteoglycans is a complex carbohydrate composed of a covalent bond between a protein and a glycosaminoglycan. The polysaccharide is generally more abundant than the proteoglycan. It is one of the main components of connective tissue and is produced by connective tissue-specific cells or fibroblasts and chondrocytes. Its main function is to embed or coat the fibrous component (collagen and elastin) of connective tissue, and it can also be used as a pad tissue to smooth the joints. Proteoglycan is a kind of glycoconjugate composed of core protein and one or more covalently linked amino glycans. It is an important component of cell membrane, basement membrane, especially extracellular matrix, and the structure of tissue cells. It is closely related to the function. Proteoglycans are a class of compounds consisting of aminoglycans and core proteins, which have a sugar content of more than 95%, and thus are more chemically similar to polysaccharides than proteins, and are actually protein-containing polysaccharides.
Proteoglycans are categorized by their relative size (large and small) and the nature of their glycosaminoglycan chains.
1. Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) consisting of a series of alternating sugars (N-acetylgalactosamine and glucuronic acid). It is commonly found to attach to proteins as part of a proteoglycan. The chondroitin chain can contain more than 100 individual sugars, each of which can be sulfated in different locations and amounts. Chondroitin sulfate is an important structural component of cartilage and has a large compressive strength. Together with glucosamine, chondroitin sulfate has become a widely used dietary supplement for the treatment of osteoarthritis.
Figure 2. Chemical structure of one unit in a chondroitin sulfate chain.
2. Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs in the form of proteoglycans (HSPG) in which two or three HS chains are attached to the cell surface or to extracellular matrix proteins. HS binds to various protein ligands (including Wnt) in this form and modulates a wide range of biological activities, including developmental processes, angiogenesis, blood clotting, detachment activity (granzyme B) eliminated by GrB, and tumor metastasis. HS has also been shown to act as a cellular receptor for a variety of viruses, including respiratory syncytial virus.
Figure 3. Structure formula of a heparan sulfate subunit.
3. Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) consisting of a series of alternating sugars (N-acetylgalactosamine and glucuronic acid). It is commonly found to attach to proteins as part of a proteoglycan. The chondroitin chain can contain more than 100 individual sugars, each of which can be sulfated in different locations and amounts. Chondroitin sulfate is an important structural component of cartilage and has a great ability to withstand stress. Together with glucosamine, chondroitin sulfate has become a widely used dietary supplement for the treatment of osteoarthritis.
Figure 4. Chemical structure of one unit in a chondroitin sulfate chain.
5. Keratin sulfate (KS), also known as keratin sulfate, is one of several sulfated glycosaminoglycans (structural carbohydrates) found especially in the cornea, cartilage and bone. It is also synthesized in the central nervous system, which is involved in both development and glial scar formation after injury. Keratin sulfate is a large, highly hydrated molecule that acts as a cushion for mechanical shock absorption in joints.
Figure 5. Chemical structure of keratan sulfate
Proteoglycans are one of the important components of the extracellular matrix. It can bind to collagen, fibronectin, laminin and elastin in the extracellular matrix to form an extracellular matrix with tissue properties. Like collagen, the extracellular matrix of different tissues contains different types and levels of aminoglycans and proteoglycans, and is compatible with its function. For example, cartilage and long bones contain more chondroitin sulfate proteoglycans. The water retention of chondroitin sulfate (determined by the polyhydroxyl group and polyanion of the glycosylation) makes it occupy a certain space and has a certain capacity, which is especially important for the growth plate of the epiphysis. The lack of chondroitin sulfate proteoglycan or insufficient sulfation of chondroitin sulfate can reduce the volume of the tarsal plate, resulting in short limb development and deformity. The polyanion of aminoglycans can bind to divalent cations (such as Ca2+), which plays an important role in the calcification of tissues, especially the deposition of bone salts.
Relationship with disease
Aminoglycans and proteoglycans in the arterial wall are intrinsic factors that cause low-density lipoprotein and calcium deposition. The content of dermatan sulfate in the arterial wall increases with age and can bind to low density lipoprotein at physiological pH and ionic strength. In the aortic tissue with atherosclerotic plaque, an abnormal increase in dermatan sulfate content is observed, which is produced by smooth muscle cells proliferating in the lesion site. Proteoglycans are also involved in the development and metastasis of tumors. In some tumors, such as stromal tumors, nephroblastoma, breast cancer and glioma, the synthesis and secretion of hyaluronic acid in tumor cells increases, and the content of hyaluronic acid in body fluids (blood, urine) increases. Has a certain diagnostic significance. The content of chondroitin sulfate is increased in tumor tissues such as liver, lung, breast, colon and prostate. In vitro experiments have shown that chondroitin sulfate promotes the growth of breast cancer; in vivo experiments have shown that it has a promoting effect on Ehrlich ascites cancer. The enzyme that degrades chondroitin sulfate inhibits the growth of Ehrlich ascites cancer.
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