Collagen Synthesis Flashcards
What is step 1?
Synthesis and entry of chain into lumen of ER. Signal peptide cleaved as protein enters the lumen.
What is step 2?
Hydroxylayion of proline/lysine residues
What is step 3?
Glycosylation (addition of N-linked oligosaccharides)
What is step 4?
Galactose added to hydroxylysine residues. After this, Chain alignment and formation of disulphide bonds between chains. (this is mainly in golgi)
What is step 5?
Cleavage of N & C procollagen terminuses to release triple helical procollagen. Note, there are hundreds of additional N and C terminal amino acids that aren’t part of the triple helix.
What is step 6?
Completion of O-linked glycosylation by addition of glucose. The molecule is then packaged into transport vesicles and exocytosis follows.
What is step 7?
Outside the cell, propeptides at N and C terminals cleaved to release tropocollagen
What is step 8?
Lateral association of collagen molecules followed by covalent cross linking
What is step 9?
Aggregation of fibrils (covalent cross links between aldehyde groups, catalysed by lysyl oxidase. Vit B6 and Cu2+ ions are cofactors)
What is the basic unit of collagen?
- Basic unit is tropocollagen
- Primary sequence is (glycine-X-Y)n
- Glycine is only amino acid small enough to fit in the helix
- X or Y are mainly proline or hydroxyproline
- 3 polypeptide alpha chains
- right handed helix for high tensile strength
- Proline residues allow for correct structure
What is the role of prolyl hydroxylase?
- associated with PDI in the ER
- requires vitamin C and Fe3+ for activity
- allows increased increase hydrogen bonding which stabilises structure.
What is scurvy due to?
-easier for chain to unravel at lower temperature due to weaker hydrogen bonding
