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Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing, where some sugars are trimmed as they pass through the Golgi cisternae.

Proteoglycans are a subclass of O-linked glycoproteins in the extracellular matrix. Repeating units of disaccharides, called glycosaminoglycans or GAGS, can be added to form long-chain sugars to form proteoglycans. GAGs are crucial for the glycocalyx, a structure that functions as a reservoir for sequestered growth factors surrounding the cell membrane. The most commonly occurring GAGs are heparan sulfate, chondroitin sulfate, and dermatan sulfate. GAGs are classified based on the number, composition, and degree of sulfation.

Proteoglycans attach to the extracellular side of the plasma membrane and conjugate with proteins forming parts of protective coats such as mucins on the mucosal epithelial cell surface. The most common O-linked glycosylation occurs in mucins as they have a high number of proline, serine, and threonine residues, thus creating many sites for O-glycosylation.

Diseases due to abnormal O-type glycosylation:

Abnormal O-linked glycosylation involving one or more glycoproteins can result in autoimmune diseases such as immunoglobulin A nephropathy, systemic lupus erythematosus, and inflammatory bowel disease. Enhanced glycosylation of multiple proteins and abnormal O-linked N-acetylglucosamine-mediated signaling result in some forms of diabetes. Abnormal O-linked mannose-mediated glycosylation can cause congenital muscular dystrophies, such as Walker–Warburg syndrome and muscle-eye-brain disease.

Tags
ProteoglycansGlycoproteinsGlycosylationO glycosylationGlycosaminoglycansGAGsExtracellular MatrixMucinsAutoimmune DiseasesDiabetesCongenital Muscular DystrophiesGlycan CompositionSignaling Pathways

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