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EXTRACELLULAR
MATRIX
Muti ullah
EXTRACELLULAR MATRIX
• Collagen and elastin are examples of common
fibrous proteins of the extracellular matrix that
serve...
COLLAGEN:
• Collagen is the most abundant protein in the
human body.
• A collagen molecule is a long structure in which
th...
• In some tissues, collagen may be dispersed as a gel
that gives support to the structure, as in the
extracellular matrix ...
TYPES OF COLLAGEN:
• The collagen superfamily of proteins has more than
25 types.
• The three polypeptide α chains are hel...
CLASSIFICATION OF COLLAGEN:
FACITs = fibril-associated collagens with interrupted triple
helices.
1. Fibril Forming Collagens:
• Types I, II, and III are the fibrillar collagens.
• They have the rope-like structure.
• Ty...
2. Network Forming Collagens :
• Types IV and VIII form a three dimensional mesh,
rather than distinct fibrils.
• For exam...
3. Fibril Associated Collagens :
• Types IX and XII bind to the surface of collagen
fibrils, linking these fibrils to one ...
Triple Helical Structure:
• Collagen although is a fibrous protein but it has an
elongated, triple-helical structure that ...
STRUCTURE:
•Amino acid sequence :
• Collagen is rich in proline and glycine, both of which are
important in the formation ...
• The glycine residues are part of a repeating sequence
–Gly–X–Y–
where
• X is frequently proline.
• Y is often hydroxypro...
Hydroxyproline and Hydroxylysine:
• Collagen contains hydroxy-proline and hydroxy-lysine,
which are not present in most ot...
Glycosylation:
• The hydroxyl group of the hydroxy-lysine residues
of collagen may be enzymatically glycosylated.
Most com...
BIOSYNTHESIS:
• The polypeptide precursors of the collagen
molecule are synthesized in fibroblasts.
• They are enzymatical...
1. Formation of pro-α chains :
• The newly synthesized polypeptide precursors of α-chains
(pre-pro-α chains) contain a spe...
2. Hydroxylation:
• The pro-α chains are processed by a number of enzymatic steps within the lumen of the
RER.
• Proline a...
3. Glycosylation:
• Some hydroxy-lysine residues are modified by
glycosylation with glucose or galactose.
4. Assembly and secretion:
• After hydroxylation and glycosylation, three pro-α
chains form pro-collagen.
• The formation ...
5. Extracellular cleavage of
procollagen molecules :
• After their release, the pro-collagen molecules are
cleaved by pro-...
6. Formation of collagen fibrils :
• Tropo-collagen molecules spontaneously associate
to form collagen fibers.
• They form...
7. Cross link formation:
• The fibers of collagen molecules serves as a substrate for lysyl oxidase.
• This copper contain...
DEGRADATION:
• Normal collagen molecules are highly stable having half lives as long as several
years.
• Breakdown of coll...
Abnormalities in Collagen:
Ehlers Danlos syndrome :
• It is a heterogeneous group of connective tissue disorder.
• It is a...
CLASSIC TYPE:
• It is due to defect in collagen type V.
• It is characterized by skin extensibility, skin fragility and jo...
Osteogenesis Imperfecta:
• This syndrome, known as brittle bone disease , is a genetic disorder of bone
fragility characte...
• This change disrupts the triple helix near the carboxy terminal, So the
polypeptide becomes excessively glycosylated and...
TYPES:
TYPE I OSTEOGENESIS IMPERFECTA:
• It is the most common form.
• It is characterized by mild bone fragility, hearing...
TYPE III OSTEOGENESIS IMPERFECTA:
• It is also a severe form.
• It is characterized by multiple fractures at birth, short ...
Visit us
• https://iaanatorg.wixsite.com/welfare
• Send us feedback
• mailto:iaanat.org@gmail.com
• Our page on facebook
•...
Extracellular matrix
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Extracellular matrix

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what is extracellular matrix, it components and their role, how they are formed.

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Extracellular matrix

  1. 1. EXTRACELLULAR MATRIX Muti ullah
  2. 2. EXTRACELLULAR MATRIX • Collagen and elastin are examples of common fibrous proteins of the extracellular matrix that serve structural functions in the body. • Collagen and elastin are found as components of skin, connective tissue, blood vessel walls, sclera and cornea of the eye.
  3. 3. COLLAGEN: • Collagen is the most abundant protein in the human body. • A collagen molecule is a long structure in which three polypeptides (referred to as “α chains”) are wound around one another in a rope-like triple helix.
  4. 4. • In some tissues, collagen may be dispersed as a gel that gives support to the structure, as in the extracellular matrix or the vitreous humor of the eye. • In other tissues, collagen may be bundled in tight, parallel fibers that provide great strength, as in tendons.
  5. 5. TYPES OF COLLAGEN: • The collagen superfamily of proteins has more than 25 types. • The three polypeptide α chains are held together by hydrogen bonds between the chains. • These α chains are combined to form the various types of collagen found in the tissues.
  6. 6. CLASSIFICATION OF COLLAGEN: FACITs = fibril-associated collagens with interrupted triple helices.
  7. 7. 1. Fibril Forming Collagens: • Types I, II, and III are the fibrillar collagens. • They have the rope-like structure. • Type I collagen fibers have supporting property of high tensile strength (for example, tendon and cornea). • Type II collagen molecules are restricted to cartilaginous structures. • Type III collagen are prevalent in more distensible tissues, such as blood vessels.
  8. 8. 2. Network Forming Collagens : • Types IV and VIII form a three dimensional mesh, rather than distinct fibrils. • For example, type IV molecules assemble into a sheet or meshwork that constitutes a major part of basement membranes .
  9. 9. 3. Fibril Associated Collagens : • Types IX and XII bind to the surface of collagen fibrils, linking these fibrils to one another and to other components in the extracellular matrix.
  10. 10. Triple Helical Structure: • Collagen although is a fibrous protein but it has an elongated, triple-helical structure that is stabilized by inter-chain hydrogen bonding.
  11. 11. STRUCTURE: •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 causes “kinks” in the peptide chain. • Glycine is found in every third position of the polypeptide chain.
  12. 12. • The glycine residues are part of a repeating sequence –Gly–X–Y– where • X is frequently proline. • Y is often hydroxyproline. • Thus , most of the α chain can be regarded as a poly- tripeptide whose sequence can be represented as (– Gly–Pro–Hyp–). • While X and Y can be any other amino acids, about 100 of the X positions are proline and about 100 of the Y positions are hydroxyproline.
  13. 13. Hydroxyproline and Hydroxylysine: • Collagen contains hydroxy-proline and hydroxy-lysine, 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. The hydroxylation is, thus, an example of post- translational modification. • Generation of hydroxy-proline maximizes formation of inter-chain hydrogen bonds that stabilize the triple helical structure.
  14. 14. Glycosylation: • The hydroxyl group of the hydroxy-lysine residues of collagen may be enzymatically glycosylated. Most commonly, glucose and galactose are sequentially attached to the polypeptide chain prior to triple helix formation.
  15. 15. BIOSYNTHESIS: • The polypeptide precursors of the collagen molecule are synthesized in fibroblasts. • They are enzymatically modified and form the triple helix, which gets secreted into the extracellular matrix. • After additional enzymatic modification, the mature extracellular collagen monomers aggregate and become cross-linked to form collagen fibers .
  16. 16. 1. Formation of pro-α chains : • The newly synthesized polypeptide precursors of α-chains (pre-pro-α chains) contain a special amino acid sequence at their N-terminal ends. • This sequence acts as a signal that forces this polypeptide (being synthesized) to be secreted from the cell. • The signal sequence helps in the binding of ribosomes to the rough endoplasmic reticulum (RER) AND • Directs the passage of the pre pro-α chain into the lumen of the RER. The signal sequence is rapidly cleaved in the RER to yield a precursor of collagen called a pro-α chain.
  17. 17. 2. Hydroxylation: • The pro-α chains are processed by a number of enzymatic steps within the lumen of the RER. • Proline and lysine residues found in the Y-position of the –Gly–X–Y– sequence can be hydroxylated to form hydroxy-proline and hydroxy-lysine residues. • These hydroxylation reactions require certain co-factors. • molecular oxygen. • Ferrous ions. • vitamin C. • In case of vitamin C deficiency, absence of hydroxylation reactions occur, due to which interchain H-bonding is impaired. • Collagen fibers are also not cross-linked, greatly decreasing the tensile strength of the assembled fiber. The resulting disease is known as scurvy.
  18. 18. 3. Glycosylation: • Some hydroxy-lysine residues are modified by glycosylation with glucose or galactose.
  19. 19. 4. Assembly and secretion: • After hydroxylation and glycosylation, three pro-α chains form pro-collagen. • The formation of pro-collagen begins with formation of interchain disulfide bonds between the C-terminal extensions of the pro-α chains. • The pro-collagen molecules move through the Golgi apparatus, where they are packaged in secretory vesicles. • The vesicles fuse with the cell membrane, causing the release of pro-collagen molecules into the extracellular space.
  20. 20. 5. Extracellular cleavage of procollagen molecules : • After their release, the pro-collagen molecules are cleaved by pro-collagen peptidases ,which remove the terminal propeptides releasing triple-helical tropo-collagen molecules .
  21. 21. 6. Formation of collagen fibrils : • Tropo-collagen molecules spontaneously associate to form collagen fibers. • They form an ordered, overlapping, parallel array, with adjacent collagen molecules arranged in a staggered pattern.
  22. 22. 7. Cross link formation: • The fibers of collagen molecules serves as a substrate for lysyl oxidase. • This copper containing extracellular enzyme deaminates some of the lysine and hydroxy-lysine residues in collagen. • The reactive aldehydes that result (allysine and hydroxyallysine) can condense with lysine or hydroxy-lysine residues in neighboring collagen molecules to form covalent cross-links and mature collagen fibers.
  23. 23. DEGRADATION: • Normal collagen molecules are highly stable having half lives as long as several years. • Breakdown of collagen fibers is dependent on the proteolytic action of enzyme collagenases. • For type I collagen, the cleavage site is specific, generating three-quarter and one-quarter length fragments . • These fragments are further degraded by other matrix proteinases .
  24. 24. Abnormalities in Collagen: Ehlers Danlos syndrome : • It is a heterogeneous group of connective tissue disorder. • It is an inheritable defect. • 10 different types are found till now. • It can be caused by: 1.Deficiency of collagen-processing enzymes a. lysyl hydroxylase b. N-procollagen peptidase 2. Mutations in the amino acid sequences of collagen types I, III, or V.
  25. 25. CLASSIC TYPE: • It is due to defect in collagen type V. • It is characterized by skin extensibility, skin fragility and joint hypermobility. VASCULAR TYPE: • It is due to defects in type III collagen. • It is the most serious form of EDS. • It is associated with potentially lethal arterial rupture.
  26. 26. Osteogenesis Imperfecta: • This syndrome, known as brittle bone disease , is a genetic disorder of bone fragility characterized by bones that fracture easily, with minor or no trauma. • It is inherited as a dominant trait. • It results due to mutation, which results in the replacement of single glycine residue by cysteine in Type I collagen. • Over 100 different types of mutations in the gene are reported.
  27. 27. • This change disrupts the triple helix near the carboxy terminal, So the polypeptide becomes excessively glycosylated and hydroxylated. • This leads to unfolding of helix and fibrillar array cannot be formed. • Which results in brittle bones leading to multiple fractures and skeletal deformities.
  28. 28. TYPES: TYPE I OSTEOGENESIS IMPERFECTA: • It is the most common form. • It is characterized by mild bone fragility, hearing loss , and blue sclerae. TYPE II OSTEOGENESIS IMPERFECTA: • It is the most severe form. • It is typically lethal in the perinatal period as a result of pulmonary complications . • In utero fractures are seen.
  29. 29. TYPE III OSTEOGENESIS IMPERFECTA: • It is also a severe form. • It is characterized by multiple fractures at birth, short stature , spinal curvature leading to a “humped-back”(kyphotic) appearance and blue sclerae. DENTINOGENESIS IMPERFECTA: • It is a disorder of tooth development which may be seen in OI.
  30. 30. Visit us • https://iaanatorg.wixsite.com/welfare • Send us feedback • mailto:iaanat.org@gmail.com • Our page on facebook • iaanat facebook page

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