7.3 Glycoconjugates: Proteoglycans,
glycoproteins, and Glycolipids
Glycoconjugate
 Roles of glycoconjugate (information carriers)
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

Signal transduction (by recognition extracellular signal or parasites)
Cell-cell & cell-ECM communications
Protein labeling for translocation and degradation
 Proteoglycan
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

Sulfated glycosaminoglycan-attached membrane proteins (cell surface)
or secreted protein (ECM)
Glycosaminoglycan is the major part
 Binding sites for other proteins (electrostatic interactions)
Major components of connective tissue providing strength and resilience
 Glycoproteins
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Oligosaccharide-attached proteins
Outer face of plasma membrane, ECM, blood
Inside cells; golgi, secretory granules, lysosomes
Specific sites for recognition (information-rich oligosaccharide)
 Glycolipids
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
Membrane sphingolipids; oligosaccharide on hydrophilic head groups
Specific site for recognition
Proteoglycan
 Roles of proteoglycan
 40 types in mammalian cells
 Tissue organizer


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Development of specialized tissues
Mediating growth factor activity
Regulating extracellular assembly of collagen fibrils
 Structure
 Core protein-tetrasaccharide bridge-glycosaminoglycan
 Secretion to ECM or integration to the membrane

e.g. Syndecans and glypicans
Proteoglycan
Domain structure of heparan sulfate
- Modulation of ligand – receptor
interactions at cell surface
- Highly sulfated domains (NS) vs.
unmodified domains (NA)
- Variation of sulfation pattern in NS
domain among proteoglycan
Heparan Sulfate
 Protein interactions with NS domains of heparan sulfate
Proteoglycan Aggregates
 Structure
 Many aggrecans + single hyaluronate
 Proteoglycan aggregates
 Mr> 2 X 108
 Function
 Strong interaction with fibrous matrix
proteins (collagen, elastin, fibronectin) in
ECM
 Tensile strength, resilience
 Anchoring cell to ECM
 Cell-cell interaction, migration
Glycoproteins
 Glycosylation to proteins
 O-linked glycosylation : Ser, Thr
 N-linked glycosylation : Asn
 Types of glycoproteins
 Membrane proteins
 Secreted proteins

Antibody, hormones, milk proteins
(lactalbumin), proteins released by
the pancreas, lysosomal proteins
 Advantages of oligosaccharide
attachment
 Hydrophilicity (polarity & solubility)
 Destination label
 Label for protein quality control
 Protein folding
 Protection from proteolytic attacks
 Informational roles (recognition &
communication)
Glycolipids and Lipopolysaccharides
 Gangliosides

Eukaryotic membrane lipid
with oligosaccharide
containing a sialic acid and
monosaccharides in the
lipid head group
 E.g. blood typing
 Lipopolysaccharides
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

Structure in the outer
surface of gram(-) bacteria
(Escherichia coli,
Salmonella typhimrium)
Prime immunological target
against bacterial infections
Some are toxic to animals
7.4 Carbohydrates as Informational Molecules :
The Sugar Code
Lectins
 Carbohydrate-binding proteins with high affinity and specificity
 Biological functions
 Cell-cell recognition/ Signaling/ Adhesion/ Intracellular targeting of
newly synthesized proteins
 Detection and separation of glycoproteins
Half-Life regulation of hormones
 Luteinizing hormone and thyrotropin
 Peptide hormones produced in the pituitary
 N-linked glycosylation ending with GalNA4S (b14)GlcNAc
 Recognized by a lectin of hepatocytes
 Uptake and degradation
 Periodic rise and fall
 Glycoproteins with sialic acid at the end
 Protected from degradation in the liver (e.g. ceruloplasmin,
erythrocytes)
 Removal of sialic acid by sialidase (neuraminidase) from old
proteins
 Recognition of unprotected Gal by asialoglycoprotein receptor
in the liver
 Endocytosis and degradation
Lectins in development of diseases
 Selectins (plasma membrane lectins)
mediating cell-cell recognition and
adhesion
 Movement of neutrophils through the
capillary wall to tissues at sites of
infection or inflammation
 P-selectin on capillary endothelial cell

surface binds to glycoprotein of
neutrophils  slow-down neutrophils
movement along the capillary
Interaction between integrin on capillary
endothelial cell surface and ligand on
neutrophils  Stops neutrophils rolling,
and begins extravasation into infected
tissue
 Mediation of inflammatory responses
- rheumatoid arthritis, asthma, psoriasis,
transplantation rejection
Lectins in development of diseases
 Hemagglutinin (lectin of influenza
virus)
 Essential for viral entry and infection
 Interaction with sialic acid residue
from host cell’s oligosaccharides
entry & bud-out
 Sialidase (neuramidase)
 Cleavage of sialic acid  releasing

viral particles
Target for antiviral drugs
e.g) Tamiflu, Relenza
 Lectins of herpes simplex viruses
 Interaction with heparan sulfate on
host cell surface
 Sulfation pattern dependency
 target for drug development
Bacterial Adhesion by Lectins
 Helicobacter pylori


Responsible for gastric ulcers
Bacterial membrane lectins
 Interaction with oligosaccharide Lewis b of
gastric epithelial cells
 Part of the type O blood group determinant
 Greater incidence of gastric ulcer in people
of blood type O
 Leb analogues as potential drugs
 Toxins (lectins)
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
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Vibrio cholerae toxin (cholera toxin)
 Attach to oligosaccharide of ganglioside GM1 on
the surface of host epithelial cell
Bordetella pertussis toxin
 Enters target cells after interacting with host
oligosaccharide with a terminal sialic acid
Toxin analogs without carbohydrate binding site as
potential vaccines
Intracellular Lectins
 Mannose 6-P receptor


Membrane-associated lectin on the lumenal
side of golgi complex
Interaction with mannose 6-P-containing
proteins
 transport vesicle to fuse lysosome
 Targeting mechanism of most enzyme in
lysosome
 ER lectins
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
Calnexin (membrane) & calreticulin (soluble)
 Induce native folding of new proteins
Protein quality control



Glycosylation as quality control signals
ERGIC53; transport folded proteins to golgi
complex (maturation)
EDEM; transport abnormally folded proteins to
cytosol (degradation)
Lectin-Carbohydrate Interactions
 Strong and specific interactions
 Hydrogen bonding
 Van der Waals interactions
 Salt bridge
Mannose-6-P with receptor
Sialic acid - Sialoadhesin
 General interactions
 Hydrophobic interactions
Roles of Oligosaccharide Recognition
and Adhesion at the Cell Surface