1. FIBROUS PROTEINS
MALIK ALQUB MD. PHD.

2. Examples of fibrous proteins
Collagen found in
Tendons, cornea, vitrous humor. Skin, cartilage, basement membrane, bone,, etc…
Elastin found in
Lungs, large blood vessels
Alpha keratins found in
Hair and nails ve

3. An electron micrograph of collagen from skin

5. The Collagen Helix
Each polypeptide chain in the collagen molecule folds into an extended alpha chains (approximately 1000 amino acids).
The amino acid sequence contains repeats of -Gly-X-Y- where X is often proline and Y is often hydroxyproline or hydroxylysine.

6. Collagen synthesis
Transcription Translation  hydroxylation  glycosylation

7. Collagen synthesis
Proper Folding  secretion  Procollagen

8. Collagen synthesis
In ECM  N- and C-terminal are cleaved cross-link formation

9. Collagen synthesis
 cross-link formation

10. Cross-link formation

11. Formation of Hydroxyproline & Hydrolysine
Posttransitional modification is important in stabilizing the collagen structure.
Absence of vitamin C in the diet reduces hydroxylation of pro, and collagen fibres begin to break down and new collagen not formed properly.
Lack of vitamin C causes scurvy because collagen fibres are not formed properly, and this causes skin lesions, weakened gums so teeth fall out etc.

12. Collagen Related Disease
Scurvy – problems with sea voyages, lack of food other than salted meats.

13. Collagen Related Disease
Several heritable diseases result from mutations in the collagen
Marfan’s Syndrom and Ehler’s-Danlos syndromes - inherited disorder of connective tissue which affects many organ systems, including the skeleton, lungs, eyes, heart and blood vessels.
All resulting from various mutation in collagen and other fibril associated proteins, ultimately affecting the structure and molecular interaction.

14. Collagen Related Disease
Several heritable diseases result from mutations in the collagen
Brittle Bone Disease – results from a Gly-Ala mutation – Consider the consequences of this mutation, both in the protein’s triple helix and the strength of the bone!

15. Hydrogen Bonding in the Collagen Triple Helix
In the regular collagen triple helix, the three chains are held close together by direct interchain hydrogen bonds between proline C=O groups and glycine NH groups.

16. Hydrogen Bonds in the Gly-Ala Mutation
In the region around the alanine residues, the three polypeptide chains are forced apart by the alanine side chains.
Four water molecules are inserted in the interior of the triple helix to mediate hydrogen bonds between the polypeptide chains, which are displaced due to the alanine side chains in this region.

17. Elastin
Composed of nonpolar amino acids; glycine, alanine, valine. Also rich in lysine.
The cross-links involve lysine to form desmosine
Elastaes degrades elastin
α1-antitrypsin inhibits the elastase
α1-antitrypsin deficiency leads to a chronic uninhibited tissue breakdown
desmosine