Proteoglycans

Proteoglycans are a class of glycoproteins composed of a core protein with one or more covalently attached glycosaminoglycan (GAG) chains. The GAGs are long, linear polysaccharides that are often sulfated, giving proteoglycans a high negative charge.

Proteoglycans are major components of the extracellular matrix (ECM) and the cell surface. They are classified as secreted ECM proteoglycans, such as aggrecan, decorin, versican, and perlecan, and as cell-surface proteoglycans, including syndecans and glypicans. A common structural feature is the tetrasaccharide linkage region that attaches GAG chains to serine residues on the core protein, followed by diverse sulfation patterns that influence interactions with other molecules.

Common GAGs include chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin, and keratan sulfate; hyaluronic acid is a unique, non-covalently associated GAG that can form aggregates with core proteins via link proteins.

Functions of proteoglycans include providing structural rigidity and hydration to tissues, influencing collagen fibrillogenesis, and regulating diffusion through the ECM. The fixed negative charges attract water and ions, forming an osmotic gel that resists compression. The sulfation patterns and GAG density modulate binding and presentation of growth factors, cytokines, and receptors, thereby affecting signaling in development, angiogenesis, wound healing, and cancer.

Alterations in proteoglycan synthesis, degradation, or sulfation are associated with diseases such as mucopolysaccharidoses, osteoarthritis, fibrosis, and tumor progression. Biosynthesis occurs in the Golgi apparatus, with proteoglycans either secreted or displayed on the cell surface, while hyaluronan can bind to proteoglycans to form large ECM aggregates.