1

Biochemistry of
connective tissue
- extracellular matrix
 2

Connective tissue

The connective tissue is formed by:

CELLS
and

EXTRACELLULAR MATRIX
(intercellular matrix)
 3

Extracellular matrix
Function
▫ stabilisation of tissue structure
▫ regulation cell behavior
• survival, development, migration, proliferation
▫ membrane filtration barrier (glomerules)
▫ exchange of different metabolites, ions and water
▫ reparation function
▫ immune processes
▫ participation in inflammation
 4

Cells of connective tissue

▫ Fibroblasts
▫ Chondroblasts (cartilage)
▫ Osteoblasts (bone)
▫ Odontoblasts (tooth)

These cells synthetise extracellular

matrix.
 5

Extracellular matrix
Parts of the extracellular matrix
• FIBRILLAR PROTEINS (collagen, elastin)
• insoluble in water, no hydratation
• GLYCOPROTEINS (e.g. fibronectin,laminin)
• GLYCOSAMINOGLYCANS AND PROTEOGLYCANS
• soluble in water, easily hydratated

Saccharide content
increases
 6

Extracellular matrix

FIBRILLARY PROTEINS

▫ Structural proteins
•collagen firmness
•elastin elast icit y
 7

COLLAGENS

The most abundant proteins in mammals.

They form approximately 25 % of all
body proteins.
 8

Collagens
Collagenum
gr. kolla glue;
gr. gennao constitute
By boiling collagen is denatured to a colloid solution (gelatine).
From the nonpurified collagen the glue arises.
Incidence
• main protein of the extracellular matrix
• component of tendons, cartilages, bones, and teeth (dentin
and cement), skin and vessels.

Properties
• fibrillary proteins
• nonsoluble (glyco-) proteins
• HIGH STRENGHT, BUT ALSO SUPPLENESS
Structure of collagen
 Collagens
Collagen has an characteristic amino acid composition
and their specific sequence.

Primary structure
• Characteristic AA composition

• Characteristic AA sequence

Mature collagen contains no tryptophan and almost no

cysteine  from the nutritional point of view not fully
valuable protein.
 Primary structure of collagen
Characteristic AA composition
• Fundamental amino acids

n
onte
▫ Glycine 33 % (x Hb 4 %)

High
c
t
▫ Proline 13 % (x Hb 5 %)

• Derived amino acids

▫ 4-Hydroxyproline 9 % (x Hb 0 %)

Chaacteristic
for collagen
▫ 5-Hydroxylysine 0,6 % (x Hb 0 %)
Origin by posttranslational modification

Hb = hemoglobin
 Primary structure of collagen
Fundamental AA
▫ Glycine

▫ Proline

• Derived AA
▫ 4-Hydroxyproline

▫ 5-Hydroxylysine
 Primary structure of collagen
Characteristic AA sequence

Triplet

– Gly – X – Y –
Glycine Proline
Hydroxyproline
(Hydroxylysine)

• Every third AA is GLYCINE

• On the next position frequently PROLINE
• On the third position frequently hydroxyproline, ev.
hydroxylysine
Primary structure of collagen
Example of AA sequence of a part of the polypeptide
chain

-Gly-Pro-Hyp-

Globular proteins rarely show periodicity

in AA sequence.
Secondary structure of collagen
Comparison of collagen helix to the -helix, which represents
the most common secondary structure in proteins.

Collagen helix -helix

• levorotatory helix (the most common secondary
• steeper rising structure in proteins)
• 3,3 AA/turn • dextrorotatory helix
• intrachain hydrogen bonds not • gradual rising
present • 3,6 AA/turn
• proline prevents formation of • stabilization by intrachain
-helix or -pleated sheet hydrogen bonds
 Triple helix
Three -chains of
collagen

Triple
helix
Relatively rigid

This structure is responsible for the tensile strenght.

 Triple helix
The origin is dependent on the oddness of the
primary structure

• High presence of glycine

▫ smallest amino acid, no side chain (only –H)

▫ placed in the centre of triple helix, where no space is

available

▫ close contact between the chains

Triple helix is stabilized by hydrogen bonds between each

peptide bond -NH group of glycine and C=O group of the
peptide bond of the adjacent polypeptide chain.
 Collagen chains
The collagen chain is extraordinarly long and contains
approximately 1000 AA.

The collagen chains are called 1  3.

▫ They differ in AA representation
▫ Products of different genes  e.g. 1(I) or 2(V)
▫ Roman digit labels the collagen type

More than 30 different types of collagen exists.

 Collagen chains
The representation of chains differs in individual types
of collagens.

The collagens may form homotrimers or heterotrimers.

Homotrimers
▫ molecule of collagen is formed by three identical chains;
▫ e.g. collagen type III is formed by three 1(III) chains
Heterotrimers
▫ molecule of collagen is formed by different chains;
▫ e.g. collagen type I is assembled of two 1(I) chains and one
2(I) chain
 Collagen synthesis

Collagen is an example of a protein, whose synthesis is

connected with many posttranslational modifications
(treatment of the polypeptide chain), which take part
intra- and extracellularly.
Synthesis and posttranslational modifications
of collagen
Synthesis of polypeptide chain

Hydroxylation of proline and some lysine residues

Glycosylation of selected hydroxylysine residues

Formation of –S-S- bonds in extension peptides

Intracellular
processes

Triple helix formation

Secretion of procollagen
Posttranslational modifications of collagen

Proteolytic removal of propeptides

Assembling of collagen fibrils

Extracellular
processes

Formation of cross-links
Posttranslational modifications in the
course of collagen synthesis

INTRACELLULAR PROCESSES
Hydroxylation of proline and lysine
residues
Enzymatically catalyzed reaction
▫ Prolylhydroxylase
Dioxygenases
▫ Lysylhydroxylase contain Fe

cofactors
•Vitamin C !!!
•-ketoglutarate

Reaction needs oxygen. One O atom forms -OH group of

hydroxyproline, the other becomes part of the originating
succinate.
Hydroxylation of the proline and lysine
residues
Reactions catalyzed by prolylhydroxylase

Dioxygenase
contains Fe

Vitamin C
Maintains Fe2+ in a
reduced state
 Hydroxylation of proline and lysine
Reaction catalyzed by prolylhydroxylase
• reaction highly specific only for proline attached in
the polypeptide chain to the amino group of the
glycine

N- end -Gly-Pro-Ser-Gly-Pro-Pro-Gly-Leu- C- end

× × Hydroxylation

-Gly-Pro-Ser-Gly-Pro-Hyp-Gly-Leu-
Hydroxylation of proline and lysine

Importance of proline and lysine residues

hydroxylation
Hydroxyproline
• necessary for origin of triple helix by formation of
hydrogen bonds between individual chains

Hydroxylysine
• glycosylation on the formed -OH group
 Deficiency of vitamin C
Nonhydroxylated chain is not able to mature

The stable triple helix cannot be formed

Immediate degradation inside the cell

Loss of collagen in the matrix

Falling out of teeth

Vascular fragility
Poor wound healing
 Vitamin C deficiency

Avitaminosis - scurvy
Manifestation of avitaminosis in oral cavity
• swollen reddish gums
• falling out of the teeth
 Glycosylation
• Attachment of galactose or galactosylglucose
to -OH group of the hydroxylysine

Enzymatically catalyzed reaction

▫ Galactosyltransferase
▫ Glucosyltransferase

Number of saccharide units depends on the type of

collagen - e.g.:
▫ Type I (tendons) – 6 units
▫ Type II (lens envelope) – 110 units
 Glycosylation
Glycosylated residue of hydroxylysine in the molecule of
collagen
NH2
Galactosyltransferase
-glycoside
H2C

bond
CH2OH
OH O CH
O
OH H2C
Glucosyltransferase OH
CH2OH CH2 O
O O
OH HN C C
H

OH OH

Mechanism of glycosylation is different than that in the

glycosylation of serine or asparagine.
 Formation of –S-S- bonds
Disulphide bonds
• in the region of C-terminal propeptides
▫ interchain and intrachain disulphide bonds

• in the region of N-terminal propeptides

▫ intrachain disulphide bonds

Importance
• necessary for initiation of triple helix formation
starts from the C-end
• secretion out of the cell
 Formation of –S-S- bonds
C- end
N- end I
S
I
S
I I
S
I
S
I

interchain
intrachain
disulphide bonds

intrachain
disulphide bonds
 Procollagen
N-end C-end

N-terminal C-terminal
propeptide
TROPOCOLLAGEN propeptide of the
of the procollagen
procollagen mature molecule of
the collagen globular
globular domain
domain

Function of propeptides
• Start the formation of triple helix in ER intracellularly.
• Prevent a premature fibril formation – extracellularly.
 Posttranslational modifications
in the process of collagen synthesis

EXTRACELLULAR PROCESSES
 Cleaving of the propeptides
Extracellular proteinase Extracellular proteinase
Aminopeptidase Carboxypeptidase
‰ PROCOLLAGEN

‰
N-terminal propeptide TROPOCOLLAGEN C-terminal propeptide
of procollagen (PINP) monomer of procollagen (PICP)

MARKERS OF BONE FORMATION

(detection in serum or in plasma)
 Tropocollagen
▫ Greek tropé - turn, induce a turn
▫ monomer of the collagen – mature molecule of collagen
▫ Mr = 300 000

TROPOCOLLAGEN
monomer

N-terminal C-terminal
telopeptide of collagen (INTP) telopeptide of collagen (ICTP)
nonhelical area of chains nonhelical area of chains

MARKERS OF BONE DEGRADATION

(detection in serum or in the urine)
 Formation of fibrils
Polymeration
Tropocollagen Collagen fibril
(spontaneous)

The way of aggregation of fibrillary collagen

• Regular arrangement along the row and in the adjacent row
• Monomers in one row are not linked end to end (gap 40 nm)
• The adjacent row is displaced by ¼ of the length
• In the arrangement of monomers act the weak noncovalent
bonds
Assembling of collagen fibrils

Tropocollagen
Polymerisatio

Collagen fibrils
n

Collagen fibers
 Formation of cross-links
Collagen fibers are stabilized by formation of the covalent
cross-links, which can be formed either within the
tropocollagen molecule between the three chains 
intramolecular cross-links and between the tropocollagen
molecules  intermolecular cross-links.
Intermolecular
cross-links

Intramolecular
cross-links
 Formation of cross-links

Function of cross-links
stabilization and strengthening of collagen fibril

Cross-linking

high breaking strength

lower extensibility
 Formation of cross-links
Character of cross-links
▫ covalent bonds

Examples
▫ aldol cross-link
•intramolecular
▫ pyridinoline a deoxypyridinoline cross-links
histidine-aldol cross-link
•intermolecular
 Aldol cross-link
▫ Cross-link on the N-end of tropocollagen is formed
between the lysine residues of two chains

Mechanism of formation
1. oxidative deamination of lysine, aldehyde formation
▫ by the enzyme lysyloxidase
▫ aminooxidase, containing Cu2+
▫ prosthetic group – pyridoxalphosphate

2. Aldol condensation of aldehyde groups

spontaneous reaction, two aldehydes form a cross-link
 Pyridinoline and deoxypyridinoline
cross-link
▫ Cross-link between N-end of one tropocollagen
molecule and C-end of the adjacent tropocollagen
molecule

Pyridinoline
▫ of 3 hydroxylysine residues

Deoxypyridinoline
▫ of 2 hydroxylysine and 1 lysine residues
▫ more specific for bone and dentine
 Pyridinoline and deoxypyridinoline
cross-links
Mechanism of origin
1. step – oxidative deamination of lysine to aldehyde
▫ catalyzed by lysyloxidase enzyme

2. step – formation of ketoamine

▫ nonenzymatic reaction of oxidized hydroxylysine
with nonoxidized lysine (hydroxylysine)


-CH-CH 2 -NH 2 + O=CH-CH-CH 2 - -CH-CH 2 -NH-CH 2 -CO-CH 2 -

OH OH OH
 Pyridinoline a deoxypyridinoline
cross-links
Hydroxyallysine
3. step – formation of the
pyridine ring
▫ Interaction of ketoamine with the
free aldehyde group of the
hydroxylysine closes the
Allysin
heterocyclic pyridine ring, linking
covalently three diferent collagen
chains
Hydroxylysine

Intermolecular cross-bridge
 Pyridinoline a deoxypyridinoline
cross-links
▫ In the course of bone degradation these cross bridges
are separated from collagen fibers, released to blood
and excreted to urine.
▫ The pyridinoline and particularly the deoxypyridinoline
bridges may be determined in blood and urine.

MARKERS OF BONE DEGRADATION

Overview of collagens - classes
Fibrillar collagens – e.g. types I, II, III, V
• „typical“ collagens forming fibrils

Collagens associated with collagen fibrils – for example types VI,

IX, XII, XIV, XVI
• Triple helix is interrupted by sections making possible the bending of the
molecule.
• These collagens attach to the surface of collagen fibrils and join them
together and connect them to other constituents of extracellular matrix

Net forming collagens – types IV, VIII and X

• Do not form typical fibrils
• Net like arrangement
• Nonhelical globular domains on the ends of the molecule
 Overview of collagens-classes

Anchoring collagens – type VII

• forms anchoring fibers
• strengthen the connection of dermis and epidermis

Transmembrane collagens – types XIII and XVII

• integral membrane proteins
 Overview of collagens
Some fibrilar collagens
Type Molecular Occurrence
structure
I [1(I)]2 [2(I)] widely present, skin, vessels,
tendons, gingiva, bone, cement, dentin,
periodontal ligaments

II [1(II)]3 cartilage, vitreous body

III [1(III)]3 skin, vessels, lungs, gingiva, cement,

dentin, periodontal ligaments

V [1(V)]3, [1(V)2 2(V)] skin, smooth muscle, bone,

cement, dentin
 Types of collagen
Some collagens associated with fibrils
Type Molecular Occurrence
structure

VI [1(VI) 2(VI) 3(VI)] laterally associated with

collagen type II, widely
present, bone, gingiva, cement,
periodontal ligaments
IX [1(IX) 2(IX) 3(IX)] laterally associated with
collagen type II, cartilage,
vitreous body, periodontal ligaments

XII [1(XII)]3 associated with collagen type I

in soft tissues,
periodontal ligaments
 Oveview of collagens
Some net forming collagens
Type Molecular Occurrence
structure

IV [1(IV)]2 [2(IV)] basal membranes,

formation of two-dimensional net
gingiva, periodontal ligaments
Disorders of collagen synthesis

Increased collagen synthesis

• fibroses

Decreased collagen synthesis

• genetic disorder
• acquired disorders
Disorders of collagen synthesis
Increased collagen synthesis - FIBROSIS
• hepatic cirrhosis
• pulmonary fibrosis
• atherosclerosis

Tissue damage stimulates collagen synthesis by

fibroblasts
▫ e.g. damaged hepatocytes are replaced by fibrous connective
tissue  hepatic cirrhosis
Disorders of collagen synthesis
Increased collagen synthesis
▫ bacterial infections also stimulate collagen
synthesis
Prevention of infection spreading  ABSCES
x
Some bacteria (Clostridia) produce
collagenases, which degrade tropocollagen.
Disorders of collagen synthesis

Decreased collagen synthesis

• Genetically conditioned
▫ Ehlers-Danlos syndrome
▫ osteogenesis imperfecta

• Acquired disturbances
▫ lathyrism
▫ copper deficiency
▫ vitamin C deficiency
Disorders of collagen synthesis

Ehlers-Danlos syndrom
▫ heterogenous group of diseases caused by defects
of enzymes necessary for synthesis of collagen or
by abnormalities in the procollagen gene
Manifestations
▫ extreme extensibility of connective tissue and skin
▫ hypermobility of joints
▫ contortionists
▫ risk of rupture of vessels or of the intestine
Disorders of collagen synthesis
Osteogenesis imperfecta
▫ group of diseases caused by mutation in collagen type I
▫ exchange of Gly for an AA having larger side chain
▫ formation of triple helix is not possible
▫ degradation of polypeptide chains not forming triple helix

Manifestations
▫ abnormal bone fragility
▫ bone fractures even in small injuries
▫ in more serious cases prenatal fractures

Lat. imperfectus incomplete

Disorders of collagen synthesis

Dentinogenesis imperfecta
▫ group of diseases caused by mutation in 1(I)
▫ associated with osteogenesis imperfecta

Manifestations
▫ thin enamel
▫ discolouring of teeth (yellow, brown, grey)
▫ opalescence of the teeth
▫ lower mechanical resistance of the teeth
Disorders of collagen synthesis
Disturbance of cross-link formation
• Causes
▫ copper deficiency (part of lysyloxidase)
▫ animal food containing -aminopropionitrile (contained
in seeds of sweet pea  Lathyris odoratus) – blocks
lysyloxidase  lathyrism

Manifestations
extreme fragility of connective tissue (bones, vessels)
 61

ELASTIN

Elastin is the main protein of elastic fibers,

providing elasticity to the tissues.
 Elastin
Occurrence
• in arteries, particularly in aorta
• in skin, tendons and loose connective tissue (relatively
low content)
• in lungs

Synthesis takes place in early development or after

tissue damage
Half-time is approximately 70 years (lower content in
elderly people).
 Elastin
Properties
EXTENSIBILITY AND CONTRACTILITY

▫ resembles the rubber

▫ after extension elastin is able to return to original size
and original form
▫ tensile strength is lower than in collagen
▫ hydrophobic, practically insoluble in aqueous solutions
 Primary structure of elastin
Occurrence of amino acids
▫ 1/3 glycine
▫ high content of nonpolar AA (Ala, Val, Leu, Ileu)
▫ low hydroxyproline
▫ no hydroxylysine  elastin is not glycosylated

Sequence of amino acids

▫ typical triplet as in collagen is not present

Alternation of short hydrophobic and hydrophilic sections.

Hydrophilic sections, which represent a minority part, are rich in
lysine, which takes part in forming of cross - links.
 Secondary and tertiary structure
of elastin
Secondary structure
▫ elastin does not form a regular secondary structure
▫ elastin has an character of random coil
conformation enabling extension and contraction

Tertiary structure
▫ a stable secondary structure is not expressed
Intracellular Elastin synthesis
Synthesis of polypeptide chain
processes

Hydroxylation of proline residues

Secretion of tropoelastin

Tropoelastin
(globular structure, Mr = 70 000)
Extracellular
processes

Formation of cross-links

Three-dimensional netting
 Cross-links in elastin
Cross-links
▫ there is a large number of covalent cross-links in elastin
▫ some are similar as in collagen
▫ key step is an oxidative deamination of some lysine residues by copper-
containing lysyloxidase (the same enzyme as in formation of cross-links
in collagen)
▫ cross-links may be formed within one polypeptide chain or between 2 – 4
chains

• Desmosine
▫ cross-link completely specific for elastin
▫ arises from 4 side chains of LYSINE (3 oxidized and 1 nonoxidized)
▫ determines the high elasticity of elastin

Linking of polypeptide chains of elastin by cross-links constitutes a three-

dimensional netting explaining the „rubber-like“ properties of elastin.
GLYCOSAMINOGLYCANS
 Glycosaminoglycans (GAG)
(Mucopolysaccharides)

Characteristic
▫ heteropolysaccharides (100% polysaccharides)
▫ not branched polysaccharide chains
▫ long chains (70 – 200 monosaccharides)
▫ repeating disaccharide units

Muco – these substances were first detected in mucus

 Glycosaminoglycans

Polysaccharide chain of GAG is formed

by repeating disaccharide units.

[URONIC ACID – AMINO SUGAR]n

OR
[MONOSACCHARIDE - SULFONATED AMINO SUGAR]n
 Glycosaminoglycans
Uronic acids present in GAG
COO
O OH
OH

OH
OH
D-glucuronic acid
 Glycosaminoglycans
Amino sugars present in GAG
 Glycosaminoglycans

Modifications of amino sugars in GAG

▫ Acetylation of aminogroup  elimination of a
positive charge
▫ Attachment of a sulphate on OH C-4 or C-6 (ester
bond), or on nonacetylated amino group  increase
of a negative charge
 Glycosaminoglycans
Characteristics
• high number of acidic groups
▫ - COO- (uronic acids )
▫ - OSO3- (amino sugars with sulphate groups)

• highly negative charge at physiological pH (polyanions)

Na + Na + Na + Na +
H20 H20 H20 H20 H20
 Glycosaminoglycans
Characteristic (cont.)
▫ chains repel each other and in solution tend to straighten
▫ negatively charged groups bind cations – Na+, K+
▫ osmotically active
▫ strongly hydrophilic (1 g proteoglycans/50 g of water)
• occupy larger volume when compared with proteins
▫ in low concentrations form hydrated gel
• determine the turgor of extracellular matrix
▫ act as a filter allowing the diffusion of small molecules (e.g. ions,
water) and prevents the diffusion of proteins and movement of
cells
 Glycosaminoglycans

Types of glycosaminoglycans
Seven types (groups) of GAG
▫ differ in occurrence of monosaccharides,
type of glycoside bond, grade and
localisation of sulphate groups
 Groups of glycosaminoglycans
Chondroitin-4-sulphate Chondroitin-6-sulphate
▫ cartilage ▫ embryonal connective tissue
▫ bone ▫ heart valves
▫ vascular wall ▫ cartilage
▫ aorta ▫ bone
▫ cornea ▫ vascular wall, aorta
▫ dentin, cement ▫ cornea
▫ gingiva, periodontal ▫ predentin, cement
ligaments ▫ periodontal ligaments

Repeating disaccharide Repeating disaccharide

GLUCURONATE GLUCURONATE
+ N-ACETYLGALACTOSAMINE-4- + N-ACETYLGALAKTOSAMINE-6-sulphate
sulphate
 Groups of glycosaminoglycans

Chondroitin-4-sulphate Chondroitin-6-sulphate

Both are the most abundant GAG in the body

Both bind collagen and firmly connect the fibrils.
Depletion of chondroitinsulphate in the cartilage is the
main cause of osteoartritis.
 Groups of glycosaminoglycans
Keratansulphate Dermatansulphate
▫ intervertebral disc ▫ predominantly in skin
▫ bone ▫ vessels, heart valves
▫ cornea ▫ tendons
▫ predentin, cement ▫ lungs
▫ periodontal ligaments ▫ gingiva, periodontal ligament
▫ cement
Repeating disaccharide
GALACTOSE +
Repeating disaccharide
IDURONATE
N-ACETYLGLUKOSAMIN-6-sulphate
+ N-ACETYLGALAcTOSAMIN-4-sulphate
No uronic acid !! Differs from chondroitin-4-sulphate only
by inverse configuration on C-5 in
glucuronate, changed by epimeration to
iduronate.
 Groups of glycosaminoglycans
Heparin Heparansulphate
▫ deposited intracellularly in ▫ extracellularly deposited
granules of mastocytes in basal membranes and
along arteries in the liver, cell surfaces
lungs and skin ▫ larger than heparin
▫ anticoagulant effect ▫ gingiva, periodontal
ligaments, cement

Repeating disaccharides
IDURONAT-2-SULPHATE + N-SULPHO-GLUCOSAMIN-6-SULPHATE
 Groups of glycosaminoglycans
Hyaluronic acid (hyaluronate)

Repeating disaccharide
GLUCURONATE + N-acetyl-GLUCOSAMIN
Both monosaccharide units are glucose derivatives.
They do not contain any sulphate groups.

• Characterized by abnormal length (up to 25 000

disaccharide units - Mr 106 – 107)
• Polysaccharide chain is coiled to levorotatory
helix stabilized by intramolecular hydrogen
bonds.
 Groups of glycosaminoglycans
Hyaluronic acid (hyaluronate)

Occurrence
▫ proteoglycan aggregates
▫ vitreous body
▫ synovial fluid (lubricating function)
▫ umbilical cord
▫ production increases during wound healing
▫ gingiva, periodontal ligaments
▫ cement
 Groups of glycosaminoglycans
Hyaluronic acid (hyaluronate) Hyualuronate
Hyaluronate unlike other GAG is not
bound covalently to any core protein.
X
Hyaluronate forms with other
proteoglycans aggregates.
Proteoglycans are attached
noncovalently to hyaluronate by the
N-end domain of the core protein
(electrostatic interaction) with the
help of link protein.
Proteoglycan
(glycosaminoglycans
and core protein)
 Glycosaminoglycans

Forms of GAG existence

• part of larger structures (proteoglycans)

• independent molecules (heparin, hyaluronate)

 PROTEOGLYCANS

Proteoglycans are formed by

glycosaminoglycans, attached to core protein.
 Proteoglycans
Glycosaminoglycan
(non branched saccharide
chain)

Proteoglycan aggregate
(proteoglycans
and hyaluronate)

Proteoglycan
(glycosaminoglycans
and core protein)

Hyualuronate
 Proteoglycans
Function of proteoglycans
❑ increase of the pressure resistance
❑ sieve for macromolecules – restriction of their
diffusion
❑ lubrication effect
❑ hydratation of joint cartilages
❑ adhesion of cells and their migration
❑ involvement in the development of cells and tissues
❑ binding of signal molecules
❑ in bone tissue – binding of calcium salts
 Proteoglycans
Glycosaminoglycans (except for hyaluronate) are
covalently bound to so called core protein.

Parts of proteoglycans
▫ Glycosaminoglycans (polysaccharides) 95 %
▫ Protein 5%

Glycosaminoglycans
Core protein
 Proteoglycans

Attachment of glycosaminoglycan chain to core

protein:
▫ O-glycoside bond
• Through the reaction of -OH group of serine or threonine
of the core protein with trisaccharide Xyl-Gal-Gal

▫ N-glycoside bond
• Through the reaction of amide nitrogen of asparagine
 Proteoglycans
• Proteoglycans are characterized by
structural diversity:
▫ different core proteins
▫ different GAG chains
▫ different length of GAG chains
• Proteoglycans differ also in localisation:
▫ proteoglycans attached to basal membrane
▫ interstitial proteoglycans
 Selected proteoglycans
Proteoglycan Typ GAG Function

Versican chondroitinsulphate forms proteoglycan

dermatansulphate aggregates with hyaluronate
• cartilage, gingiva
Aggrecan chondroitinsulphate
keratansulphate
• binds to collagen
• belongs to a group of small
Decorin chondroitinsulphate
proteoglycan rich in leucine
dermatansulphate • gingiva

• present in basal membrane

• long core protein
• forms a barrier limiting
Perlecan heparansulphate penetration of
macromolecules through the
basal membrane
 Selected proteoglycans
Proteoglycan Occurrence in tissues of oral cavity

Versikan periodontal ligaments,

cement
Aggrecan

periodontal ligaments,
Decorin cement, dentine

Perlecan development of different tissues

 93

ADHESION GLYCOPROTEINS

Ensure specific interactions between cells

and molecules of extracellular matrix.
 94

Adhesion glycoproteins
• Functions of adhesion glycoproteins
▫ attachment of cells to extracellular matrix
▫ organization of the compounds of extracellular
matrix

• Long flexible molecules with several binding sites

for:
▫ collagen
▫ other matrix proteins
▫ polysaccharides
▫ cell receptors (integrins – cell adhesion receptors)
 95

Adhesion glycoproteins
• Selected representatives of adhesion
glycoproteins
▫ fibronectin
▫ laminin
▫ osteonectin
▫ chondronectin
 96

Adhesion glycoproteins
• Fibronectin
▫ Formed by two subunits arranged to the shape of
letter V
▫ Binding sites for:
• collagen,
• heparansulphate,
• hyaluronate
• integrins

▫ Functions as a connection of cells in extracellular

matrix containig fibrillary collagen
 97

Adhesion glycoproteins
• Laminin
▫ Formed by three different chains arranged to the
shape of cross
▫ High relative molecular mass Mr = 950 000
▫ Binding sites for:
• collagen of type IV
• heparansulphate,
• hyaluronate,
• cell adhesion receptors

▫ Adhesion glycoprotein of the basal membrane –

connect collagen type IV and other compounds of
the membrane