3. COLLAGENCOLLAGEN
is the mainis the main proteinprotein of connective tissue inof connective tissue in
animals and the most abundant protein inanimals and the most abundant protein in
mammals, making up about 25% of themammals, making up about 25% of the
total protein contenttotal protein content
5. Collagens illustrates diverseCollagens illustrates diverse
structure-function relationshipsstructure-function relationships
Collagen of tendons – forms highly asymmetric structures of high
tensile strength
Skin collagen – forms loosely woven, flexible fibers
Collagen of hard regions of teeth & bone – contains
hydroxyapatite, a calcium phosphate polymer
Collagen in the cornea – nearly crystalline, transparent
COLLAGENCOLLAGEN
6. Tropocollagen is a Triple Helical moleculeTropocollagen is a Triple Helical molecule
Rich in Gly, Pro, and HypRich in Gly, Pro, and Hyp
TropocollagenTropocollagen-- consist of 3 approximately 1000-residue
polypeptide chains organized as left-handed non-α-helix
that has approximately three residues per turn.
Three left-handed helices entwine to form a right-handed
triple helix, or supercoil stabilized by hydrogen bonds
formed between individual polypeptide chains.
COLLAGENCOLLAGEN
7. TropocollagenTropocollagen
The supercoil resists unwinding because it and its
three polypeptides are coiled in opposite directions.
The highly asymmetric mature collagen fibers
measures 1.5 nm by about 300 nm, reflecting their
stable, extended conformation.
COLLAGENCOLLAGEN
Spatial arrangement of atoms.
It can change only by rotating bonds, no bonds are broken.
8. α chains coiled about each other into a right-handed triple helixes
9. Every third residue is GlycineEvery third residue is Glycine
(Gly-X-Pro/Hyp)n
The primary structural motif of mature collagen.
Every 3rd
residue is Glycine, the only residue with an R group
small enough to fit within the central core of the superhelix.
Each Glycine is preceded by either a Prolyl or Hydroxyprolyl
residue.
COLLAGENCOLLAGEN
10. COLLAGENCOLLAGEN
Many Posttranslational modificationsMany Posttranslational modifications
Characterize Procollagen maturationCharacterize Procollagen maturation
Procollagen
collagen precursor with the carboxyl and amino terminals have an amino acid
composition typical of a globular protein.
During maturation of procollagen, these carboxyl and amino terminal
extensions are removed by selective proteolysis.
Hydroxylation of prolyl and lysyl residues is catalyzed by prolyl hydroxylase
and lysyl hyroxylase – enzymes that require ascorbic acid (vit. C)
Specific hydroxylysyl residues are then glycosylated by galactosyl and glucosyl
transferases.
11. Covalent cross-links stabilize collagen fibersCovalent cross-links stabilize collagen fibers
Tropocollagen associate to form collagen microfibrils.
Stabilized by
intrachain hydrogen bonds
Covalent bonds formed within & between helices
*This covalent cross-linking process involves the copper-requiring enzyme
lysyl oxidase, which converts the non-α-amino groups of hydroxyl residues
to aldehydes.
*These aldehydes then either undergo an aldol condensation or condense
with the non-α-amino groups of lysine or hydroxylysine, forming Schiff
bases.
COLLAGENCOLLAGEN
12. Nutritional an Genetic disordersNutritional an Genetic disorders
Can involve impaired secondary structureCan involve impaired secondary structure
The medical importance of stable secondary structures
is thoroughly documented by disorders of
tropocollagen biosynthesis and maturation.
COLLAGENCOLLAGEN
13. Severe Vitamin C deficiency
-prolyl & lysyl hydroxylases are inactive and tropocollagen cannot
undergo the reactions that form covalent cross-links which results to scurvy
SCURVY- nutritional disorder characterized by bleeding gums, poor wound
healing, an ultimately death.
Menke’s disease
is caused by a defective gene that regulates the metabolism of copper in the
body. Because it is an X-linked gene, the disease primarily affects male
infants. Copper accumulates at abnormally low levels in the liver and brain,
but at higher than normal levels in the kidney and intestinal lining. Affected
infants may be born prematurely, characterized by kinky hair and growth
retardation’
COLLAGENCOLLAGEN
14. Genetic disorders of collagen biosynthesis include several form
of osteogenesis imperfecta characterized by fragile bones.
Ehlers-Danlos syndrome characterized by mobile joints and
skin abnormalities, reflect defects in the genes that -encode α1-
procollagen, procollagen N-peptidase, or lysyly hydroxylase.
COLLAGENCOLLAGEN
