Collagen

Question 1

Name 2 pathways that proteins may be delivered to the plasma membrane

Answer 1

Regulated or constitutive

Question 2

How relatively abundant is collagen in comparison to other proteins in the body?

Answer 2

It is the most abundant protein at 25-35%
The most abundant fibrous protein in connective tissue - tendons, ligaments, cartilage, bone
Loose connective tissue providing structure to internal organs

Question 3

What type of cell secretes collagen fibres?

Answer 3

Fibroblasts

Question 4

What is the base unit of collagen? Describe it

Answer 4

Tropocollagen
300nm rod-shaped protein
3 polypeptide alpha chains, ~1000aa long
Glycine in every 3rd position along each chain (Gly-X-Y)n
Right handed triple helix

Question 5

What are the properties of the triple helix?

Answer 5

Non extensible
Non compressible
High tensile strength

E.g. In ligaments

Question 6

Why is glycine repeated in the triple helix?

Answer 6

It is the only amino acid with a side chain small enough to fit in the middle of the helix

Question 7

In the triple helix (Gly-X-Y)n characteristic repeat, what are commonly in the X and Y positions?

Answer 7

Proline or hydroxyproline

Question 8

What stabilises the structure of the triple helix?

Answer 8

H bonds between the alpha chains

Question 9

Describe the distribution of collagen types

Answer 9

I - (2 alpha 1, 1 alpha 2), Skin, tendon, ligaments, bone, 90% of all body collagen

II - (3 alpha 1) Cartilage, intervertebral discs

III - (3 alpha 1) Foetal skin, cardiovascular system

IV - (2 alpha 1, 1 alpha 2) Basement membrane

V - (2 alpha 1, 1 alpha 2) Placenta, skin

Question 10

Describe the synthesis and modification of collagen in the ER

Answer 10

Collagen has a signal sequence when first made - targeted to ER - initial form is called PREPROCOLLAGEN (pre refers to signal)
Entry of the chain into RER lumen
Cleavage of signal peptide - PROCOLLAGEN
Hydroxylation of selected proline and lysine residues
Addition of N-linked ogliosaccharides
Addition of galactose to hydroxylysine residues
Chain alignment and formation of disulphides bonds (in C terminal region - triple helix starts to form)
Formation of triple helix from C to N

Question 11

What is prolly hydroxylase?

Answer 11

Enzyme allows addition of hydroxyl group to make hydroxyprolines - increased H bonds - if not then interactions in triple helix are weaker - denatured at much lower temps

Associated with PDI in the ER
Requires vitamin C and Fe2+ ions for activity
Scurvy is due to weak tropocollagen triple helices

Question 12

Describe procollagen secretion from the ER

Answer 12

Completion of O linked ogliosaccharide chains by addition of glucose
Transport vesicle
Exocytosis
Removal of N and C terminal propeptides - about 150 on N and 250 on C - these formed disulphides bonds earlier - these tend to stop the mature collagens coming together
Peptidases remove these ends leaving TROPOCOLLAGEN

Question 13

Describe the formation of collagen fibre

Answer 13

Propeptides removed to leave tropocollagenLateral association of collagen molecules followed by covalent cross linking - staggered array of tropocollagen
Aggregation of fibrils
Covalent bonds link tropocollagen together by lysines

Question 14

What is Lysyl oxidase

Answer 14

Forms covalent cross links between tropocollagen
Extracellular
Requires vitamin B6 and Cu2+ ions for activity

Question 15

What is Ehlers-Danlos syndrome?

Answer 15

Mutation of collagen type V or Lysol oxidase deficiency - weaker collagen