Post on 31-Mar-2015
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).
Locations of Collagens (Skin)
Locations of Collagens (Basement Membranes)
LOCATIONS OF COLLAGEN (VASCULAR SYSTEM)
LOCATIONS OF COLLAGENS
BONESTEETHCARTILAGE
LOCATIONS OF COLLAGENS (TEETH)
LOCATIONS OF COLLAGENS (EYE)
Posterior Polymorphous Corneal Dystrophy
One cause is a dominantly acting mutation in a gene encoding for
collagen VIII (COL8A2). Ref: Coupal et al.
Osteogenesis imperfecta
Blue sclerae of an OI victimCaused by genetic mutations in
collagen genes COL1A1, COL1A2
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
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.
Collagens: primary structureAlmost every third residue is
glycineApprox 17% is prolineContains hydroxyprolineContains hydroxylysine (which
can form interchain bonds or be glycosylated)
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.
Collagen – Hydroxylation of Proline
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.
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.
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
Collagen – A Triple Helix
Figure 6.16 Poly(Gly-Pro-Pro),a collagen-like right-handedtriple helix composed of threeleft-handed helical chains.
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
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.
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
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.
LYSYL HYDROXYLATION
MINERALIZATION
SYNTHESIS – ASSEMBLY OF A COLLAGEN MOLECULE
SPECIFICITY OF CHAIN ASSOCIATION
EXTRACELLLULAR PROCESSING OF COLLAGEN
FIBER ARCHITECTURE
CROSS-LINKS IN A FIBERPHYSICAL STABILITY
FIBROUS COLLAGEN SUMMARY
INDUSTRIAL AND CLINICAL USES OF COLLAGENDenatured collagen (gelatin): FOODS COATINGS CAPSULESNative collagen: SURGICAL DRESSINGS IMPLANTS TISSUE ENGINEERING
PREPARATION FOR CROSS-LINKING
REACTIONS FOR CROSS-LINKS