MCBG S9 Collagen

Question 1

What is the difference between regulated and constitutive secretion?

Answer 1

Regulated secretion proteins are secreted - when signalling molecules docks on receptor.
Constitutive secretion - continuous secretion from a cell - independant of external signalling.

Question 2

Give examples of proteins in both pathways?

Answer 2

Regulated

• Insulin
• Glucagon
• ACTH
• Beta-endorphin

Constitutive

• Immunoglobins
• Albumin
• Prohormones
• Procollagen

Question 3

What is the basic unit of collagen?

What does its quarter army structure consist of?

What can be said about its primary structure?

Answer 3

Tropocollagen

Homotrimer - right handed triple helix of 3 alpha chains.

Glycine is in every 3rd position
(Gly-X-Y)n repeat
Mainly proline and hydroxyproline in the X and Y positions.

Question 4

What is the structural relevance of glycine being repeated every 3rd position?

Why can so many hydrogen bonds form and what do these do to the structure of collagen?

Answer 4

Glycine R group is small enough to fit into the middle of the triple helix.
Larger R group would disrupt procollagen packing.

Due to the extra OH groups on hydroxyproline.

Question 5

Where can collagen types I-V be found?

Answer 5

I - Skins, tendons and ligaments
II - Reticulin - in hyaline and elastic cartilage
III - CVS and foetal skin 
IV - Basement membranes
V - Placenta, skin

SCABS

Question 6

Describe the synthesis and post-translational modification of collagen that occurs inside the ER.

Answer 6

Polypeptide into ER and signal cleaved by signal peptidase.
- Prepro alpha chains to pro alpha chains
Hydroxylation of proline and lysine
- Prolyl hydroxylase
N-linked glycosylation -oligos to Asp residues
O-linked glycosylation - galactose to hyLys
Chain alignment -disulfide bonds at C and N termini - protein disulfide isomerase
Triple helix formed - procollagen now
- not at 250 C AAs and 150 N AAs

Question 7

Describe the post-translational modification of collagen that occurs in the Golgi.

Answer 7

Completion of O-linked glycosylation.
- O - glucose added to galactose of hyLys residues.

Packages into transport vesicle
Exocytosis

Question 8

Describe the post-translational modification of collagen that occurs extracellularly.

Answer 8

Removal of N and C terminal propeptides.
- where disulfide bonds were
- procollagen peptidases
Lateral association of tropocollagen by cross linking forming fibrils
- Aldo cross links
- Cross links formed by lysyl oxidase.
Aggregation of fibrils form fibre.

Question 9

What is the role of lysyl oxidase?

What vitamins/ minerals does it require?

What does deficiency of lysyl oxidase lead to and what syndrome?

What else can cause this syndrome?

Answer 9

Forms covalent cross links between tropocollagen molecules called Aldo’s cross links.
- Specifically lysine residues.

B6 and Cu2+

Weaker collagen due to insufficient or weaker tropocollagen cross linking.

Ehlers-Danlos Syndrome
Mutation in type V collagen,

Question 10

What is the role of Prolyl hydroxylase?

What vitamin and mineral does it require for activity?

Why does deficiency of the vitamin lead t

Answer 10

Hydrolysed proline and lysine residues

Vitamin C and Fe2+

Fewer hydroxyproline residues therefore fewer H bonds - weaker tropocollagen triple helices and weaker collagen
Scurvy results.