1. 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).

2. Locations of Collagens (Skin)

3. Locations of Collagens (Basement Membranes)

4. LOCATIONS OF COLLAGEN (VASCULAR SYSTEM)

5. LOCATIONS OF COLLAGENS
BONES
TEETH
CARTILAGE

6. LOCATIONS OF COLLAGENS (TEETH)

7. LOCATIONS OF COLLAGENS (EYE)
The lens capsule is a smooth, transparent basement membrane that completely surrounds the lens. The capsule is elastic and is composed of collagen.

8. Posterior Polymorphous Corneal Dystrophy
One cause is a dominantly acting
mutation in a gene encoding for
collagen VIII (COL8A2). Ref: Coupal et al.

9. Osteogenesis imperfecta
Blue sclerae of an OI victim
Caused by genetic mutations in collagen genes COL1A1, COL1A2

10. COLLAGEN TYPES 27 types with 45genetically distinct chains:
1.Fiber-forming collagens:
the quantitatively predominate collagens
chains form several molecular species:
(Types I, II, III, V, and XI) + (XXIV and XXVII)
procollagen to collagen conversion
fibers constructed of staggered, side to side,
parallel association of molecules

11. 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.

12. Collagens: primary structure
Almost every third residue is glycine
Approx 17% is proline
Contains hydroxyproline
Contains hydroxylysine (which can form interchain bonds or be glycosylated)

13. Collagen – A Triple Helix
Principal 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.

14. Collagen – Hydroxylation of Proline

15. 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.

16. 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.

17. A case of structure following composition
The Collagen Triple Helix
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

18. Collagen – A Triple Helix
Figure Poly(Gly-Pro-Pro),
a collagen-like right-handed
triple helix composed of three
left-handed helical chains.

19. Staggered arrays of tropocollagens
Collagen Fibers
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

20. Collagen – A Triple Helix
Figure 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.

21. Pro and HyP suit the constraints of φ and ψ
Structural basis of the collagen triple helix
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

22. 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.

23. LYSYL HYDROXYLATION

24. MINERALIZATION

25. SYNTHESIS – ASSEMBLY OF A COLLAGEN MOLECULE

26. SPECIFICITY OF CHAIN ASSOCIATION

27. EXTRACELLLULAR PROCESSING OF COLLAGEN

28. FIBER ARCHITECTURE

29. CROSS-LINKS IN A FIBER PHYSICAL STABILITY

30. FIBROUS COLLAGEN SUMMARY

31. INDUSTRIAL AND CLINICAL USES OF COLLAGEN
Denatured collagen (gelatin):
FOODS
COATINGS
CAPSULES
Native collagen:
SURGICAL DRESSINGS
IMPLANTS
TISSUE ENGINEERING

32. PREPARATION FOR CROSS-LINKING

33. REACTIONS FOR CROSS-LINKS