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

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

Mr > 2x10 8 Take up a volume equivalent to a bacteria cell e.g. Aggrecan core protein bound to chondroitin sulfate & keratan sulfate; Many copies bound to a single molecule of Hyaluronate Proteoglycan aggregates –Supramolecular assemblies –Many core proteins bound to a single molecule of hyaluronate Proteoglycan aggregates Associate with collagen in extracellular matrix of cartilage, contribute to the development and tensile strength of cartilage

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

Glycoproteins –Carbohydrate-protein conjugates –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) 2. Glycoproteins

Common core: 2 GlcNAc + 3 Man

High mannose type Complex type

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

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

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

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