Collagen

Question 1

Which is the most abundant protein in mammals?

Answer 1

Collagen

Question 2

Give 3 examples of where collagen is found

Answer 2

skin, bone, tendon, teeth, cartilage, blood vessels

Question 3

Why is collagen seen as ‘scaffolding’ in the body?

Answer 3

It often holds cells together in basement membranes, and has a direct role in developing tissue

Question 4

Why are there so many different types of collagen?

Answer 4

Different peptide chains are incorporated into tropocollagen

Question 5

Which types of collagen are the most common and what is their main role?

Answer 5

types 1, 2 and 3; they form long fibrils in bone and tendon

Question 6

What do network forming collagens from? (types 4 and 5)

Answer 6

from a 2D lattice to with cells can bind e.g. basal lamina

Question 7

What do fibril associated collagens form? (types 5, 9 and 13)

Answer 7

Associated with major forms and are involved in cross linking collagen molecules.

Question 8

How many polypeptide chains are in each collagen molecule?

Answer 8

3

Question 9

Where are post-translational modifications and the formation of the triple helix pro collagen formed?

Answer 9

Fibroblasts (active cells in connective tissue)

Question 10

What modifications to collagen occur in the extracellular space?

Answer 10

Removal of extension peptides, tropocollagen, aggregation to microfibril, cross linking to form collagen fibre

Question 11

What is unusual about the primary structure of collagen?

Answer 11

There is a GLYCINE residue every 3rd residue, and a repeating sequence of (gly - x - y) where x is often proline and y is often hydroxyproline

Question 12

Why must hydroxylysine and hydroxyproline be incorporated into the collagen molecule?

Answer 12

Hydroxyproline is involved in hydrogen bond formation which helps to form the helix
Hydroxylysine are attachment sites for sugar residues and are involved in covalent cross linking between collagen chains

Question 13

Which enzymes and which co-factor are used in the formation of hydroxylysine and hydroxyproline?

Answer 13

Propel hydroxylase and Lysyl hydroxylase 
Ascorbic acid (vitamin c)

Question 14

Describe the secondary structure of a collagen polypeptide

Answer 14

A left-handed helix (looks like an alpha helix). 3.3 residues per turn. Packed tightly because there is a small glycine every 3rd residue

Question 15

Describe the quaternary structure of collagen

Answer 15

Three polypeptide chains form a triple helix with a right handed twist. Glycine (hydrophobic) pack into the centre, hydroxyproline and hydroxylusine residues are on the outside

Question 16

Why does collagen have such a high tensile strength?

Answer 16

The two helices are wound in opposite directions, and the small glycine residues allow the chain to twist tightly

Question 17

How is collagen assembled into fibrils?

Answer 17

Extension peptides attach at the end of the protein strands to hold them in line while disulphide bonds form between c-terminal extensions on cysteine residues. Peptidase enzymes remove extension enzymes after the collagen has been secreted to the extracellular space. Tropocollagen spontaneously forms into fibrils, which is stabilised by covalent cross links between chains.

Question 18

How do covalent cross links form between tropocollagens in the fibril?

Answer 18

Covalent ross links are made by modified lysine residues. Lysyl oxidase removes the amine group and replaces it with an aldehyde (COH) to change lysine to allysine. Cross links then form between lysine and allysine or allysine and allysine residues. The different chains are staggered.

Question 19

What is deposited in the pores between tropocollagen molecules in the fibrils? Why?

Answer 19

Calcium, in nucleation sites for bone formation

Question 20

What is the general structure of a tendon?

Answer 20

Lots of collagen fibrils arranged into collagen fibres, which makes a large bundle = high tensile strength.

Question 21

What is the view of a collagen molecule through an electron microscope?

Answer 21

Ribbed appear, because of end to end protein chains. You can see through the molecule at different points.

Question 22

Is collagen a stable molecule?

Answer 22

Yes, half life of a few months

Question 23

What is the role of collagenases? What is their structure?

Answer 23

They break down collagen when necessary e,g, after pregnancy.
They have a metal ion (e..g zinc) in the active site

Question 24

Why are collagenases produced by tumor cells for metastasis?

Answer 24

They penetrate basement membranes of cells so the tumour can spread

Question 25

How are collagenases used in Dupuytren;’s contracture? (collagen production affects the muscle function of the hand, seizes up)

Answer 25

Collagenases can be injected into the connective tissue to breakdown excess collagen

Question 26

How does a collagen mutation affect the patient in Ehlers-Danlos Syndrome?

Answer 26

There is a lysyl oxidase deficiency which affects cross linking == joint hypermobility and stretchy skin

Question 27

How does a collagen mutation affect the patient in Scurvy?

Answer 27

There is a failure to hydroxylate lysine and proline because of a LACK OF ASCORBIC ACID (vit C) which means collagen is structurally unstable == muscle and joint pain, tiredness

Question 28

What is the mutation causing osteogenesis imperfecta?

Answer 28

A mutation in the collagen type 1 alpha 1 gene (1A1), in which a glycine residue is replaced with an arginine. Arginine is larger (where a small glycine is normally every 3rd residue), so the triple helix does not form properly. Collagen is weaker and bones snap.

Question 29

Is osteogenesis imperfecta a genetic disorder?

Answer 29

It is often a spontaneous mutation, family history is often not present.