Elastic
Collagen fibres
fibre
F
Connective Tissue
ssel
d ve
Bloo
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General Features
• Matrix
– Large amount of intercellular (extracellular) substance
• Fibers (also called “formed” elements)
– Mostly protein, but in some cases combined with other substances
• Ground substance (“Amorphous”)
– Complex chemical composition
• Cells
– One principal type of cells produces matrix
– Other cell types may be present
The devil is in the details
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Matrix
• Fibers
– Fibrillar collagens
– Elastins
– Fibronectins
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Matrix
• Ground substance
– Proteoglycans
• “Bottle-brush” structure
• Core protein with glycosaminoglycans (GAGs)
• GAGs – long chain polysaccharides (unusual)
• Many with negatively charged portions
• Hyaluronic acid – a huge GAG
• Proteoglycans bind with collagen, retain water
– Glycoproteins
• Carbohydrates attached to protein molecules (protein
predominates)
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COLLAGEN
• Collagen is the most abundant protein in the
human body
• A typical collagen molecule is a long, rigid
structure in which three polypeptides
"α-chains" are wound around one another in
a rope-like triple-helix
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Types of collagen
• The collagen superfamily of proteins includes
more than 25 collagen types, and
proteins that have collagen-like domains.
• The three polypeptide α-chains are held
together by hydrogen bonds between the
chains.
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Structure of collagen
1. Amino acid sequence:
• Collagen is rich in proline and glycine, both of
which are important in the formation of the
triple-stranded helix.
• Proline → facilitates the formation of the
helical conformation of each α-chain because
its ring structure → "kinks" in the peptide
chain.
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• The glycine residues are part of a repeating
sequence. —Gly—X—Y—, where X is
frequently proline and Y is often hydroxyproline
or hydroxylysine
• Most of the α.- chain can be regarded as a
polytripeptide whose sequence can be
represented as (—Gly—X—Y—) 333
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2. Triple-helical structure
• Unlike most globular proteins that are
folded into compact structures,
collagen, a fibrous protein, has an
elongated, triple-helical structure that
places many of its amino acid side
chains on the surface of the
triple-helical molecule.
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• Collagen contains hydroxyproline (hyp) and
hydroxylysine (hyl), which are not present in
most other proteins.
• These residues result from the hydroxylation
of some of the proline and lysine residues
after their incorporation into polypeptide
chains
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ELASTIN
• In contrast to collagen, which forms fibers
that are tough and have high tensile
strength, Elastin is a connective tissue
protein with rubber-like properties.
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• Elastic fibers composed of elastin and
glycoprotein microfibrils are found in the
lungs, the walls of large arteries, and
elastic ligaments.
• They can be stretched to several times
their normal length, but recoil to their
original shape when the stretching force is
relaxed.
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A. Structure of elastin
• Elastin is
– an insoluble protein polymer
– synthesized from a precursor,
tropoelastin, ( a linear polypeptide composed
of about 700 amino acids that are primarily
small and nonpolar) (e.g. glycine, alanine,
and valine).
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• Elastin is also,
– rich in proline and lysine,
– contains a little hydroxyproline
– contains no hydroxylysine.
• Tropoelastin is secreted by the cell into the
extracellular space.
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[Link]
Glycosaminoglycans (GAGs)
• GAGs are large complexes of negatively charged
heteropolysaccharide chains
• They are generally associated with a small
amount of protein, forming proteoglycans,
which typically consist of over 95 percent
carbohydrate
• GAGs have the special ability to bind large
amounts of water producing the gel-like matrix
that forms body's ground substance 21
Structure of GAGs
• GAGs are long, unbranched,
heteropolysaccharide chains
generally composed of a repeating
disaccharide unit
•(Asidic sugar-Amino Sugar)n
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Amino Sugar
• The amino sugar is either
– D-Glucoseamine or
– D-Galactoseamine
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•The amino group is usually
acetylated, thus eleminating
its positive charge
•The amino sugar may also be
sulfated on carbon 4 and 6 or
on a nonacetylated nitrogen
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•The acidic sugar is a uronic
acid either
–D-Glucuronic acid
–L-Iduronic acid
•The single exception is Keratan
Sulfate, in which galactose
rather than an acidic sugar is
present 26
•The acidic sugars contain
carboxyl groups that are
negatively charged at
physiologic pH and, together
with the sulfate groups, give
glycoseaminoglycans their
strongly negative nature
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Relationship between glycosaminoglycan
structure and function
• Because of negative charges, GAG chains tend
to be extended in solution
• They repel each other and are surrounded by
water molecules
• They "slip" each other, as two magnets with
the same polarity
• This produces the "slippery" consistency of
mucous secretions and synovial fluid.
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• When a solution of GAGs is
compressed, the water is "squeezed
out" and the GAGs are forced to
occupy a smaller volume
• When the compression is released,
the GAGs bring back to their
original, hydrated volume because
of the repulsion of their negative
charges
• This property contributes to the
resilience of synovial fluid and the
vitreous humor of the eye
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Classification of the
glycosaminoglycans
• The six major classes of
glycosaminoglycans are divided
according to
– type of glycosidic linkages, and
– degree and location of sulfate units.
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Glycosaminoglycans
Involved in a variety of extracellular functions; chondroitin
is found in tendons, cartilage and other connective tissues
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Glycosaminoglycans
A characteristic of glycosaminoglycans is the presence
of acidic functionalities (carboxylate and/or sulfates)
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Glycosaminoglycans
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Hyaluronic Acid
• Hyaluronic acid contains
alternating residues of
D-glucuronic acid and
N-acetylglucosamine.
• It has a molecular
weight of several
millions
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• Hyaluronic acid forms clear, highly viscous
solutions that serve as lubricants in the
synovial fluid of joints and give the vitreous
humor of the vertebrate eye its jellylike
consistency
• It is also a component of the extracellular
matrix of cartillage and tendons
• It contributes tensile strength and elasticity as
a result of its strong noncovalent interactions
with other component of matrix
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Proteoglycans
• GAGs, are found covalently attached to
protein, forming proteoglycan monomers
• Mammalian cells can produce 40 types of
proteoglycans
• Proteoglycans act as tissue organizers, and
they influence various cellular activities such
as
– growth factor activation and
– adhesion.
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• Many
proteoglycans
are secreted into
the extracellular [Link]
matrix, but some +Interactions+between+cells+and+the+extracellular+[Link]
are integral
membrane
proteins
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[Link]
1. Structure of Proteoglycan Monomers
• A proteoglycan monomer
found in the cartilage consists
of a core protein to
which the linear GAG chains
are covalently
attached.
• These chains extend out from
the core protein and remain
seperated from each other [Link]
rush%E2%80%[Link]
because of charge repulsion
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Linkage between the
carbohydrate chain and the
protein
• This linkage is most commonly
through a trihexoside
(Galactose-Galactose-Xylose)
and a serine residue),
respectively
• An O-glycosidic bond is
formed between the xylose
and a hydroxyl group of the
serine
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2. Proteoglycan Aggregates
• The proteoglycan monomers associate with a
molecule of hyaluronic acid to form
proteoglycan aggregates
• The association is not covalent, but occurs
primarily through ionic interactions
between the core protein and the
hyaluronic acid
• The association is stabilized by additional small
proteins called link proteins 42
Proteoglycan aggregates
[Link]
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[Link] 44
Mucopolysaccharidosis
• The Mucopolysaccharidosis
are hereditary disorders that
are clinically progressive
• They are characterized by
accumulation of GAGs in
various tissues, causing
varied symptoms, such as
skeletal and extracellular
matrix deformities, and [Link]
mental retardation
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• Mucopolysaccharidoses are caused by a
deficiency of one of the lysosomal
hydrolases normally involved in the
degradation of
– Heparan sulfate and/or
– Dermatan sulfate
• This results in the presence of
oligosaccharides in the urine, because of
incomplete lysosomal degradation of GAGs
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• Hurler Syndrome
• Hunter Syndrome
• Sly Syndrome
• Sanflippo Syndrome
• All of the deficiencies are autosomal and
recessively inherited except Hunter
Syndrome, which is X-linked
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Glycoproteins
• Glycoproteins are proteins to which
oligosaccharides are covalently attached
• The glycoprotein carbohydrate chains are
often branched instead of linear, and may or
may not be negatively charged
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•Glycoproteins contain highly
variable amounts of
catbohydrate
• For example: IgG contains less than four
percent of its mass as carbohydrate,
whereas human gastric glycoprotein
(Mucin) contains more than eighty percent
carbohydrate
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Structure of Glycoprotein
Oligosaccharides
• The oligosaccharide components of glycoproteins
are generally branched heteropolymers
composed primarily of D-Hexoses, with the
addition in some cases of neuraminic acid, and of
L-Fucose
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Structure of linkage between
carbohydrate and protein
• The oligosaccharide may be attached to the
protein through an N- or O- glycosidic link
• In N- glycosidic link the sugar chain is attached
to the amide group of an asparagine side
chain
• In O- glycosidic link the sugar chain is attached
to a hydroxyl group of either serine or
threonine side chain
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Serine or threonine O-linked saccharides
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Aspargine N-linked glycoproteins
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• A glycoprotein may contain only one type of
glycosidic linkage or may have both O- and
N-linked oligosaccharides within the same
molecule
• In the case of collagen, there is an
O-glycosidic linkage between
– Galactose or Glucose and the
– hydroxyl group of hydroxylysine
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O-Linked Oligosaccharides
• The O-linked oligosaccharides may have one
or more of a wide variety of sugars arranged
in either a linear or a branched patern
• Many O-linked oligosaccharides are found as
membrane glycoprotein components or
in extracellular glycoproteins
– For Example: O-linked oligosaccharides help
provide the ABO blood group determinants
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N-Linked Oligosaccharides
• The N-linked oligosaccharides fall into two
broad classes:
– Complex oligosaccharides
– High-mannose oligosaccharides
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• The complex oligosaccharides
contain a diverse group of additional
sugars suc as
– N-acetyglucoseamine,
– L-fucose,
– N-acetylneuraminic acid
• High mannose oligosaccharides
contain primarily mannose
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Some of the oligosaccharides found in N-linked glycoproteins
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Q&A
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