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BCH2011: Textbook summary - Lecture 24

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LECTURE 24 Glycoconjugates: Proteoglycans, Glycoproteins, and Glycosphingolipids: Polysaccharides and oligosaccharides are information carriers. Some provide communication between cells and their extracellular surroundings; others label proteins for transport to and localization in specific organelles, or for destruction when the protein is malformed or superfluous; and others serve as recognition sites for extracellular signal molecules or extracellular parasites. On almost every eukaryotic cell, specific oligosaccharide chains attached to components of the plasma membrane form a carbohydrate layer (the glycocalyx), that serves as an information-rich surface that is cell shows to its surroundings. These oligosaccharides are central players in cell-cell recognition and adhesion, cell migration during development. Blood clotting, the immune response, wound healing, and other cellular processes. In most of these cases, the informational carbohydrate is covalently joined to a protein or a lipid to form a glycoconjugate, which is the biologically active molecule. Proteoglycans: They are macromolecules of the cell surface or ECM in which one or more sulfated glycosaminoglycan chains are joined covalently to a membrane protein or a secreted protein. The glycosaminoglycan chain can bind to extracellular proteins through electrostatic interactions between the protein and negatively charged sugar moieties on the proteoglycan. Proteoglycans are major components of all extracellular matrices. Some proteoglycans can form proteoglycan aggregates, enormous supramolecular assemblies of many core proteins all bound to a single molecule of hyaluroan. Aggregan core protein has multiple chains of chondroitin sulfate and keratan sulfate, joined to Ser residues in the core protein through trisaccharide linkers. Aggregan interacts strongly with collagen in the ECM of cartilage, contributing to the development, tensile strength, and resilience of this connective tissue. Interwoven with these enormous extracellular proteoglycans are fibrous matrix proteins such as collagen, elastin, and fibronectin, forming a cross-linked meshwork that gives the whole extracellular matrix strength and resilience. Proteoglycans Are Glycoaminoglycan-Containing Macromolecules of the Cell Surface and ECM: The basic proteoglycan unit consists of a ‘core protein’ with covalently attached glycosaminoglycan(s). The point of attachment is a Ser residue, to which the glycosaminoglycan is joined through a tetrasaccharide bridge. Many proteoglycans are secreted into the ECM, but some
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