Collagen Flashcards

1
Q

What is collagen?

A

Family of fibrous proteins that form insoluble fibres

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2
Q

What property makes them appropriate for bone, tendon, cartilage etc

A

High tensile strength

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3
Q

Structure?

A

Consists of 3 polypeptide chains. These vary between collagen types

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4
Q

1ary structure

A

Every 3rd residue is Gly. Repeating sequence is Gly-X-Y. X is usually Pro (Gly-Pro-Y) and Y is usually Lys (Gly-X-Lys)

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5
Q

Why is every 3rd residue Gly?

A
  • Every 3rd residue of each polypeptide passes through centre of triple helix
  • Gly is the amino acid with the smallest side chain so is only one that can fit in centre
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6
Q

What happens when Gly residue is replaced with an amino acid with a larger side chain during a mutation?

A

Helix can no longer wind so tightly, leads to ineffective collagen

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7
Q

2ary structure

A

Each polypeptide chain forms a left-handed helix with 3.3 residues per turn (collagen helix)

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8
Q

What is normal amount of residues per turn?

A

3.6

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9
Q

3ary structure

A
  • 3 polypeptide chains lie parallel and twist round each other
  • This forms triple helix (right handed)
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10
Q

What is name of triple helix?

A

Procollagen (before removal of extension peptides)

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11
Q

Where is collagen finally secreted into?

A

Extracellular spaces of connective tissue

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12
Q

When do post-translational modifications occur?

A

Occurs before polypeptide chains form helix

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13
Q

Which residues are hydroxylated?

A

Proline and Lysine

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14
Q

What are the products of this hydroxylation?

A

Hydroxyproline (Hyp) and Hydroxylysine (Hyl)

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15
Q

What enzymes are involved in hydroxylation?

A

Prolyl hydroxylase and lysyl hydroxylase

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16
Q

What is required as co-factor?

17
Q

What causes scurvy?

A

Vitamin C deficiency; Hyp and Hyl and not synthesised. Results in weakening of collagen fibres

18
Q

Symptoms of scurvy

A

Skin lesions, fragile blood vessels, poor wound healing

19
Q

What is name of structure after post-translational modifications?

A

Procollagen (triple helix)

20
Q

What are extension peptides?

A

Collagen chains are synthesised with additional amino acid chains at each end (N & C termini)

21
Q

What forms between C-terminal extensions of neighbouring polypeptide chains?

A

Disulphide bonds

22
Q

What enables these bonds to form?

A

Extensions often contain Cys

23
Q

What is purpose of these bonds?

A
  1. Facilitates triple helix assembly

2. Help prevent premature aggregation

24
Q

When are extension peptides removed?

A

Removed after secretion into extracellular space.

25
How are extension peptides removed?
Removed by peptidase enzymes
26
How are fibrils formed?
After extension peptides are removed, tropocollagen aggregate and form fibrils
27
What are fibrils stabilised by?
Covalent cross-links
28
Where do covalent cross-links act?
Between and within tropocollagen molecules (hold chains together)
29
Why are these covalent cross-links not disulphide bonds as commonly found in proteins?
Lack of Cys in final mature collagen
30
What is Osteogenesis Imperfecta?
Brittle bone disease; inherited. Increased risk of bone fracture
31
What causes OI?
Spontaneous mutation in Type I collagen chains
32
What enzymes break down collagen?
Collagenase enzymes
33
How do tumour cells utilise collagenase enzymes?
They often secrete collagenase enzymes to help them destroy the connective tissue surrounding tumours (help in tumour invasion and metastasis)
34
When does procollagen become tropocollagen?
Once extension peptides are removed (after secretion)
35
What is Ehlers-Danlos Syndrome?
Collagen deficiency (deficiency in lsysl oxidase) so cross-links aren’t formed properly (weak) Symptoms: hypermobile joints, hyperextensibility of skin, extreme fatigue
36
What is Dupuytren's Contracture?
Caused by excess collagen production affecting connective tissue of hand, causing tendons in hand to contract and little finger and ring finger curve over
37
What has recently be used to treat Dupuytren's Contracture?
Injection of collegenase to break down excess collagen