L20- Collagen formation

Question 1

collagen molecules come together to form

Answer 1

fibres and fibrils

Question 2

how are collagen molecules joined together

Answer 2

covalently cross-linked

Question 3

where are collagen fibres formed

Answer 3

outside the cell (otherwise would cause the cell to apoptose)

Question 4

basic unit of collagen is

Answer 4

tropocollagen

Question 5

tropocollagen

Answer 5

o 3 x 300nm rod-shaped proteins (alpha chains- 1000 aa)
Forms triple helix (NOT ALPHA HELICAL STRUCTURE LIKE DNA)

Hydrogen bonds between the chain- stabilises the structure

Right hand

Question 6

features of tropocollagen

Answer 6

• Non- extensible- Non-compressible- High tensile strength

Question 7

collagen is an example of a

Answer 7

fibrous molecule

Question 8

tropomysosin and glycine

Answer 8

o Glycine in every 3rd positions along each alpha chain (Gly-X-Y)n repeat Glycine (only Hydrogen as R group)- smallest amino acid- a larger aa would not fit Mostly proline and hydroxyproline in X and some Y positions

Question 9

collagen is an example of

Answer 9

a post-translationally modified, secreted protein

Question 10

outline how collagen is synthesised

Answer 10

1) Collagen starts being translated by free ribosome
2) Signal sequence (found in N terminus) translated from mRNA- which targets it to the ER for secretion
3) SRP binds to newly synthesised polypeptide halting translation
4) Newly synthesised polypeptide translocated to the ER-SRP receptor recognition
5) Signal peptide sequence is removed by signal peptidase (prepro-alpha chains –> pro-alpha chains)
6) Hydroxylation of selected proline and lysine residues (prolyl hydroxylase)
7) addition of N-linked oligosaccharides- glycosylation
8) addition of galactose to hydroxylysine residues
9) protein folding (ER) starts to occur
10) formation of triple- helical procollagen from C to N terminus - pro collagen secretion (N-terminal and terminal amino acids do not form triple helix)
11) molecules gets transferred to the golgi
12) more sugar added
13) packaged into vesicle for exocytosis for exocytosis at PM
14) when pro collagen is secreted removal of N and C terminal (Procollagen –> tropocollagen)
15) tropocollagen molecules come together to form collagen fibrils through covalent cross lining (formed by lysine oxidase)
16) fibrils aggregate to form collagen fibres

Question 11

prolyl hydroxylase

Answer 11

adds hydroxyl group onto proline

• Associated with PDI in the ER
• Requires vitamin C and Fe2+ ions for activity (scurvy)
• Allows increased H bonding to stabilise triple helix
• Scurvy is due to weak tropocollagen triple helices

Question 12

pro collagen peptidase

Answer 12

chops off the N and C terminal peptides

Question 13

lysine oxidase

Answer 13

forms strong covalent cross links (extracellular) between tropocollagen molecules

Question 14

Why are N and C terminals taken off outside the cell

Answer 14

Otherwise the collagen fibres would aggregate inside the cells and cause it to burst (Important the process doesn’t happen in the cell)

Question 15

scurvy

Answer 15

• Connective tissue defect

* Due to collagen misfolding- vitamin C (prolyl hydroxylase)

Question 16

Ehler’s-Danlos syndrome (EDS)

Answer 16

Mutation in collagen type V or Lysyl oxidase deficiency