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MALIK ALQUB MD. PHD. FIBROUS PROTEINS

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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

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collagen An electron micrograph of collagen from skin

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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.

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Collagen synthesis Transcription Translation hydroxylation glycosylation

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Collagen synthesis Proper Folding secretion Procollagen

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

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Collagen synthesis cross-link formation

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Cross-link formation

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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.

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

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Collagen Related Disease Marfans Syndrom and Ehlers-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. Several heritable diseases result from mutations in the collagen Several heritable diseases result from mutations in the collagen

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Collagen Related Disease Several heritable diseases result from mutations in the collagen 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 proteins triple helix and the strength of the bone!

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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.

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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.

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Elastin desmosine Composed of nonpolar amino acids; glycine, alanine, valine. Also rich in lysine. The cross-links involve lysine to form desmosine Elastaes degrades elastin 1-antitrypsin inhibits the elastase 1-antitrypsin deficiency leads to a chronic uninhibited tissue breakdown