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COLLAGEN CHEMISTRY AND BIOLOGY
DEFINITION:
A protein with chains containing repetitive Gly-X-Y sequences allowing formation of molecules with triple-helical domains.
The triple-helical domains as well as nontriple-helical domains of the molecules interact to form multimolecular aggregates that function primarily as structural elements in extracellular spaces.
Collagens are the most abundant protein in mammals (25% of protein mass).
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Locations of Collagens (Skin)
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Locations of Collagens (Basement Membranes)
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LOCATIONS OF COLLAGEN (VASCULAR SYSTEM)
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LOCATIONS OF COLLAGENS
BONESTEETHCARTILAGE
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LOCATIONS OF COLLAGENS (TEETH)
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LOCATIONS OF COLLAGENS (EYE)
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Posterior Polymorphous Corneal Dystrophy
One cause is a dominantly acting mutation in a gene encoding for
collagen VIII (COL8A2). Ref: Coupal et al.
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Osteogenesis imperfecta
Blue sclerae of an OI victimCaused by genetic mutations in
collagen genes COL1A1, COL1A2
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COLLAGEN TYPES27 types with 45genetically distinct
chains:
1.Fiber-forming collagens: the quantitatively predominate collagenschains form several molecular species:
(Types I, II, III, V, and XI) + (XXIV and XXVII)
procollagen to collagen conversionfibers constructed of staggered, side to side,
parallel association of molecules
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COLLAGEN TYPES, CONT.2. Fiber-associated collagens:
(IX, XII, XIV, XVI, XIX, XX, XXI, XXII)
3. Network collagens (IV, VIII, X)
4. Filament collagen (VI)
5. Anchoring fibril collagen (VII)
6. Transmembrane collagens:
(XIII, XVII, XXIII, XXV)
7. Multiplexins (XV, XVIII)
Characteristics: 1) smaller and often numerous helical domains;
2) procollagen to collagen conversion (seldom);
3) staggered, side to side and antiparallel association when aggregates are formed.
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Collagens: primary structureAlmost every third residue is
glycineApprox 17% is prolineContains hydroxyprolineContains hydroxylysine (which
can form interchain bonds or be glycosylated)
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Collagen – A Triple HelixPrincipal component of connective tissue
(tendons, cartilage, bones, teeth) Basic unit is tropocollagen:
◦ Three intertwined polypeptide chains (1K residues each)
◦ MW = 285,000 ◦ 300 nm long, 1.4 nm diameter ◦ Unique amino acid composition, including
hydroxylysine and hydroxyproline◦ Hydroxyproline is formed by the vitamin C-
dependent prolyl hydroxylase reaction.
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Collagen – Hydroxylation of Proline
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Scurvy (Vitamin C deficiency)
Scorbutic gums due to of scurvy. Notice gingival red triangles.
Vitamin C is needed for post translational amino acid modifications in collagen.
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Collagen – A Triple Helix
The secrets of its a.a. composition...
Nearly one residue out of three is Gly
Proline content is unusually high Unusual amino acids found:
◦4-hydroxyproline ◦3-hydroxyproline ◦5-hydroxylysine ◦Pro and HyPro together make 30% of res.
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A case of structure following composition
The unusual amino acid
composition of collagen is unsuited for alpha helices or beta sheets
It is ideally suited for the collagen triple helix: three intertwined helical strands
Much more extended than alpha helix, with a rise per residue of 2.9 Angstroms
3.3 residues per turn Long stretches of Gly-Pro-Pro/HyP
The Collagen Triple Helix
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Collagen – A Triple Helix
Figure 6.16 Poly(Gly-Pro-Pro),a collagen-like right-handedtriple helix composed of threeleft-handed helical chains.
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Staggered arrays of tropocollagens
Banding pattern in EMs with 68 nm repeat
Since tropocollagens are 300 nm long, there must be 40 nm gaps between adjacent tropocollagens (5 x 68 = 340 nm)
40 nm gaps are called "hole regions" - they contain carbohydrate and are thought to be nucleation sites for bone formation
Collagen Fibers
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Collagen – A Triple Helix
Figure 6.17 In the electron microscope, collagen fibers exhibit alternating light and dark bands. The dark bands correspond to the 40-nm gaps between pairs of aligned collagen triple helices.
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Every third residue faces the crowded center of the helix - only Gly fits here
Pro and HyP suit the constraints of φ and ψ
Interchain H-bonds involving HyP stabilize helix
Fibrils are further strengthened by intrachain lysine-lysine and interchain hydroxypyridinium crosslinks
Structural basis of the collagen triple helix
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The hole regions of collagen fibrils may be the sites of nucleation for bone mineralization
A disaccharide of galactose and glucose is covalently linked to the 5-hydroxyl group of hydroxylysines in collagen by the combined action of galactosyltransferase and glucosyltransferase.
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LYSYL HYDROXYLATION
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MINERALIZATION
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SYNTHESIS – ASSEMBLY OF A COLLAGEN MOLECULE
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SPECIFICITY OF CHAIN ASSOCIATION
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EXTRACELLLULAR PROCESSING OF COLLAGEN
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FIBER ARCHITECTURE
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CROSS-LINKS IN A FIBERPHYSICAL STABILITY
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FIBROUS COLLAGEN SUMMARY
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INDUSTRIAL AND CLINICAL USES OF COLLAGENDenatured collagen (gelatin): FOODS COATINGS CAPSULESNative collagen: SURGICAL DRESSINGS IMPLANTS TISSUE ENGINEERING
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PREPARATION FOR CROSS-LINKING
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REACTIONS FOR CROSS-LINKS