9.2 Collagen

Question 1

Proteins are delivered to plasma membrane in two ways, what are they and give examples

Answer 1

1. Constitutive secretion
   - released all the time
   - e.g. Collagen
2. Regulated secretion
   - released when required
   - e.g. Insulin

Question 2

What is the basic unit in collagen?

Answer 2

Tropocollagen

Question 3

What shape do collagen fibres form when put together?

How many fibres form this?

Answer 3

Right handed triple helix

3 alpha polypeptide chains

Question 4

Three properties of collagen molecule.

Answer 4

1. Non-compressible
2. Non-extensible
3. High tensile strength

Question 5

What repeat of amino acids forms a collagen fibre?

Answer 5

(Gly-X-Y)n repeat

Question 6

In (Gly-X-Y)n repeat that forms a collagen fibre, why is Glycine used? What amino acids are usually in positions X and Y?

Answer 6

Glycine side chain is H and is small so can fit in the middle of the helix

X and Y are mostly proline and hydroxyproline
Allows increased H bonding to stabilise triple helix (OH grps)

Question 7

In (Gly-X-Y)n repeat, mostly proline and hydroxyproline amino acids are present. Hydroxyproline is not a conventional amino acid, so where does it come from?

Answer 7

Proline gets hydroxylated (OH added) post translationally in the ER.
Prolyl hydroxylase
Requires vit C and Fe2+ ions for activity

Question 8

What is Scurvy?

Answer 8

CT not as strong due to lack of strength in collagen. Not enough Vit C in diet! (which contributes to prolyl hydroxylase function when hydroxylating proline amino acids for our collagen fibre repeats)

Question 9

Process of synthesis and modification of collagen in endoplasmic reticulum?

Answer 9

1. Synthesis and entry of AA chain into lumen of rER
2. Cleavage of signal by signal peptidase
3. Hydroxylation of selected proline and lysine residues
4. Glycosylation (N-linked)
5. Chain alignment by disulphide bonds that covalently link ends of peptides
6. Formation of triple helix from N to C terminus (note 150, 250 AA at N and C terminus respectively that do not form helix, stay unhelixed)
7. ER buds off and goes to golgi completing O-linked Glycosylation
8. Procollagen molecular secreted in transport vesicle - exocytosis
9. Removal of N and C terminus propeptides forming tropocollagen
10. Lateral association of tropocollagen molecules and covalent cross linking forming collagen fibril
11. Aggregation of fibrils forming our collagen fibre

Question 10

In the lateral association of tropocollagen molecules, what amino acids do cross links form between?

Answer 10

Lysine residues by Lysyl oxidase

Requires vit B6 and Cu2+ ions for activity

Question 11

Where is Lysyl oxidase situated? Why?

Answer 11

Extracellular

Because we dont want collagen fibres forming inside cells!

Question 12

What is marfans syndrome?

Answer 12

Genetic disorder of body CT
Fibrillin gene affected
Essential role in maintaining strength and structural integrity of CT
V. Tall individuals - arachnodactyl