Glycoconjugates

1. Glycoconjugates Carbohydratescovalently linked to a protein or lipid Proteoglycans Glycoproteins Glycolipids act as informational carrier in: cell-cell recognition, cell-cell adhesion, cell migration, immune response, ….

2. Glycoconjugates: 1. Proteoglycans • Proteoglycans: major components of connective tissues • Macromolecules of the cell surface and extracellular matrix • Composition • A core protein (integral membrane protein or extracellular) • Glycosaminoglycans covalently attached to the protein (through Ser) • Main fraction by mass • Main site of biological activity • Example: syndecan core protein with 3 Heparan sulfate and 2 Chondroitin sulfate chains (bind cell surface receptors) Trisaccharide linker

3. Proteoglycan aggregates Associate with collagen in extracellular matrix of cartilage, contribute to the development and tensile strength of cartilage • Proteoglycan aggregates • Supramolecular assemblies • Many core proteins bound • to a single molecule of hyaluronate Mr > 2x108 e.g. Aggrecan core protein bound to chondroitin sulfate & keratan sulfate; Many copies bound to a single molecule of Hyaluronate Take up a volume equivalent to a bacteria cell

4. Extracellular meshwork • Formed by extracellular proteoglycans interwoven with fibrous matrix proteins (collagen, elastin, fibronectin) and plasma membrane proteins • Roles: • Anchor cells to extracellular matrix • Direct migration of cells in developing tissues • Convey information in and out of cells across the plasma membrane

5. 2.Glycoproteins • Glycoproteins • Carbohydrate-proteinconjugates • Carbohydrate moieties are smaller (in many cases) & more structurally diverse • Linking point: anomeric C of reducing end N- or O-linked to protein • N-linkage: Asn • O-linkage: Ser/Thr • N-linked oligosaccharides contain a common core • 2 N-acetylglucosamine (GlcNAc) • 3 mannose (Man) • Additional sugars attached to the core in many different ways • High mannose type • Complex type • GlcNAc, galactose, L-fucose • and Sialic acid (negatively charged)

6. Common core: 2 GlcNAc + 3 Man

7. High mannose type Complex type

8. Glycoprotein - Glycophorin An erythrocyte plasma membrane protein: 16 glycoxylation sites: [15 O-glycoxyl linkage (Ser/Thr) and 1 N-glycoxyl linkage (Asn)] Rich in sialic acid

9. Biological Roles of Glycans in Proteins • In early secretory pathway of glycoproteins in ER • Promote protein folding • Some proteins are completely dependent on glycosylation • Some are partially dependent • Others are not dependent on glycans • Some are glycan-dependent in one cell type but not in another • Some glycosylation sites are more important than others • Aid in certain sorting events • In later secretory pathway of glycoproteins in Golgi • Structural features of glycans act as destination labels (secreted, membrane proteins, lysosomal proteins…) • In final mature forms (intra- or extracellular locations) • Cell-cell recognition and adhesion

10. 3. Glycolipids and Lipopolysaccharides • Glycolipids: • e.g.: Gangliosides • Membrane lipids of eukaryotic cells • Head group is a complex oligosaccharide containing sialic acid in addition to other monosaccharides • Oligosaccharides contribute to the different blood groups • Lipopolysaccharides • Occurs on the outer membrane of gram-negative bacteria (e.g.: E. coli, Salmonella typhimurium) • Prime targets of antibodies • Some bacterial polysaccharides are toxic to humans

11. Bacterial Lipopolysaccharides Principal determinant of serotype (immunologic reactivity) Endotoxin; inherent to Gram-negative bacteria (E.coli; Salmonella typhimurium) Permeability barrier: Selective passage of nutrients and exclusion of harmful substances