Download Bacterial Cell Walls Contain Peptidoglycans

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Transcript
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
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
e.g. Aggrecan core protein
bound to chondroitin sulfate
& keratan sulfate;
Many copies bound to a single
molecule of Hyaluronate
Mr >
2x108
Take up a
volume equivalent
to a bacteria cell
• 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
2. 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)
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
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