Treasa's Structure and Function

Question 1

Briefly explain the steps in normal collagen synthesis.

Answer 1

Intracellular
Transcription of mRNA in the nucleus
* Genes for pro-a1 and pro-a2 chains are transcribed
Translation
* mRNA moves into the cytoplasm and interacts with ribosomes for translation.
* After translation, it is referred to as pre-pro-polypeptide chain; this chain then travels to the endoplasmic reticulum (ER) for post-translational modification.
Post-translational modification
* Once in the ER, the pre-pro-polypeptide undergoes post-translational processing where three major modifications are made to the pre-pro-polypeptide for it to become pro-collagen.
1. The signal peptide on the N-terminal is removed
2. The lysine and proline residues get additional hydroxyl groups added to them via hydroxylase enzymes which require vitamin C as a cofactor
3. Glycosylation of the selected hydroxyl groups on lysine with galactose and glucose b
* Three of the hydroxylated and glycosylated pro-a-chains assemble by twisting into a triple helix by zipper-like folding. The triple helix configuration is 3 left-handed helices twisted into a right-handed coil
* Now the pro-collagen molecule is ready to move to the Golgi apparatus for final modifications and assembled into secretory vesicles to enter the extracellular space
Extracellular
Propeptide cleavage
* Enzymes known as collagen peptidases preform propeptide cleavage and remove the ends of the procollagen molecule and the molecule becomes tropocollagen
Collagen Fibril Assembly
* Lysyl oxidase a copper-dependent enzyme acts on lysine and hydroxylysines, and covalent bonding between tropocollagen molecules form a collagen fibril