Term
Collagens are composed of.... |
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Definition
a left-handed triple helix structure whose basic motif arrangement is GLY-X-Y |
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Term
The presence of 4-hydroxyprolines ... |
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Definition
-at least 100 residues/chain increase the stability of the triple helix.
-–Any decrease in the number of hydroxyprolines leads to a decrease in the “melting” temperature of the collagen-i.e. the collagen becomes susceptible to thermal denaturation, rendering the collagen susceptible to proteolytic attack.
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Term
Post-translational modifications are very important in collagen structure
(proline and lysine hydroxylation) |
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Definition
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–The enzyme(s) responsible for proline (and lysine) hydroxylation are mixed function oxidases. Critical cofactors in the function of these enzymes include iron and ascorbic acid.
– Interfering with hydroxylase activity ultimately leads to the generation of a defective collagen fiber that is poorly secreted and tends to be easily degraded. The resultant disease is known as SCURVY.
–The generation of hydroxylysines during collagen synthesis is important in the subsequent extracellular formation of lysine cross links by lysyl oxidase.
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Term
Post-translational modifications are very important in collagen structure.
(formation of COOH terminal Disulfide Bonds)
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Definition
–is important in the initial stabilization of the triple helix.
•Osteogenesis imperfecta (one type)
–Mutations in the a2[I] collagen gene causing a frameshift in the a2[I] gene leading to the loss of cystine residues in the COOH propeptide. As result, the pro a2[I] chain misfolds and cannot be incorporated into the trimer.
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–RESULT: collagen fibrils that are secreted are [a1[I] ]3 homotrimers. The unicorporated a2[I] ultimately gets degraded. The homotrimers do not properly substitute for the type I heterotrimer.
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–This particular mutation causes severe bone abnormalities.
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Term
Post-secretory modifications are important in collagen fibril formation |
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Definition
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–Cleavage of the N and C terminal propeptides must occur for normal fibril formation.
–Ehler Danlos syndrome-Dermatosparaxis subtype (rare)-defective collagen fibril formation due to the absence of the N-procollagen peptidase enzyme. Leads to skin fragility, sagging, joint laxity. (autosomal recessive disorder)
-Reminder: Covalent cross-linking occurs after fibril assembly via the actions of lysyl oxidase. This cross linking is important for developing strength in the collagen fibrils.
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