Transcript of MALIK ALQUB MD. PHD. FIBROUS PROTEINS. Examples of fibrous proteins Collagen found in Tendons,...
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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