THE COLLAGENS

Report
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
BONES
 TEETH
 CARTILAGE

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 victim
Caused by genetic mutations in collagen genes
COL1A1, COL1A2
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
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 structure
Almost every third residue is glycine
 Approx 17% is proline
 Contains hydroxyproline
 Contains hydroxylysine (which can form
interchain bonds or be glycosylated)

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.
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.
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
Collagen – A Triple Helix
Figure 6.16 Poly(Gly-Pro-Pro),
a collagen-like right-handed
triple helix composed of three
left-handed helical chains.
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

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.
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
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 FIBER
PHYSICAL STABILITY
FIBROUS COLLAGEN SUMMARY
INDUSTRIAL AND CLINICAL
USES OF COLLAGEN
Denatured collagen (gelatin):

FOODS

COATINGS

CAPSULES
 Native collagen:

SURGICAL DRESSINGS

IMPLANTS

TISSUE ENGINEERING

PREPARATION FOR CROSSLINKING
REACTIONS FOR CROSS-LINKS

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