Collagen

Question 1

What are some characteristics of collagen?

Answer 1

Family of fibrous proteins found in all multicellular organisms.

28 types in humans, coded by 42 genes

Major proteins in bone, tendon and skin and the most abundant protein at 25% protein mass

Question 2

How does the alignment of collagen fibres change from skin to mature bone and cornea?

Answer 2

Skin - layers at right angles to each other

Bone/cornea -same arrangement

Question 3

Each collagen molecule comprises of three (a) chains forming a (b)

can be composed of one or more (a) chains such as (c) and (d)

Answer 3

a - alpha

b - triple helix

c - homotrymer

d - heterotymer

Question 4

What is the composition of Type I collagen?

Answer 4

Chains from 2 different genes:
[ alpha 1 (I)] 2 and
[alpha 2 (I)]

Question 5

What is the composition of Type II and Type III collagen respectively?

Answer 5

Both only have one chain type.

[alpha 1 (II)]3

[alpha 1 (III)]3

Question 6

What is the characteristic collagen triple helix structure?

Answer 6

Three alpha chains form it.

Glycine, proline, hydroxyproline repeat

(glycine is small so occupies the interior of the helix - H side chain)

Question 7

How are Collagen fibres assembles, smallest unit to largest?

Answer 7

One alpha chain
Three alpha chains
Collagen fibril (10-200nm)
Collagen fibre (0.5-3um)

(check histology for transverse and cross section)

Question 8

What is procollagen?

Answer 8

Collagen with non-collagenous areas at N and C termini. (left and right ends)

these are removed after secretion for fibrillar collagens but remain for others

Question 9

What gives collagen fibrils their tensile strength?

Answer 9

covalent crosslinks using lysine and hyodroxy lysine. between collagen helixes.

The regularity and extent of crosslinks changes with age

Question 10

Why does Vitamin C deficiency compromise tissue stability?

Answer 10

VC and Fe2+ needed for prolyl and lysis hydroxylases.

Lysine and proline hydroxylation contributes to interchain hydrogen bond formation fformation

Question 11

What post translational modification happens for lysine and hyroxylysine?

Answer 11

Modified in formation of covalent crosslinkages once collagen has been secreted.

Question 12

Where is Collagen made?

Answer 12

mainly in the fibroblast cells

Once procollagens; the growing peptide chains are co-translationally transported into the lumen of the rough endoplasmic reticulum (ER).

Question 13

What are Ehlers- Danlos syndromes?

Answer 13

EDS are inherited connective tissue disorders. stretchy skin and loose joints

mutations in collagen usually, affect production, structure or processing

e.g. brittle bone

Question 14

What are some Fibril associated collagens?

Answer 14

IX and XII. will form fibrils and regulate the organisation of collagen fibrils

Question 15

Collagen type IV is non-fibrillar, describe its assembly?

Answer 15

Collagen monomer forms a dimer, self assembles into tetramer and soon creates a supramolecular aggregate. Used in basement membranes

it is a network - forming collagen ! present in all basement membranes, though its arrangement moleculary can vary

Question 16

What are Fibronectins?

What is their structural makeup?

Answer 16

Multi-adhesive Gylcoproteins in matrix and body fluids. Can be insoluble fibrillar matrix or soluble plasma proteins

Large multidomain molecule linked together by disulphide bonds. 500kD dimer is the basic unit

Question 17

How are different fibronectins formed if they are derived from a single gene?

Answer 17

Alternate splicing of mRNAs giving rise to different types

Question 18

What roles do Fibronectins play? (4)

Answer 18

Regulating cell adhesion (binds ligands e.g. collagen to integrin) and migration in variety of processes (embryogenesis and tissue repair)
Wound healing and blood clot promoting

Question 19

What do Integrin receptors do?

Answer 19

At cell surface provide linkage between matrix and cell cytoskeleton

Question 20

What are Proteoglycans?

Answer 20

The core proteins with covalently attached one or more GAG chains

Can be grouped as:

Basement membrane proteoglycans (perlecan)

Aggregating Proteoglycans (aggrecan)

Leucine rich proteoglycans (Decorin)

Cell surface proteoglycans (syndecans)

Question 21

What are GAG chains

How do they contribute to the water in the ECM

Answer 21

Glycosaminoglycan chains

repeating disaccharide units with one sugar an amino sugar. Sulphated or carboxylated so have a high negative charge.

negative charge attracts cations including Na+ resulting in water being sucked into matrix

Question 22

Cartilage has large amounts of GAGs trapped in matrix, so why are collagen fibres needed?

Answer 22

GAGS cause swelling pressure. This is negated by the tension in collagen fibres creating tensile strength

Question 23

How are GAG chains grouped?

Answer 23

based on repeating disaccharide unit:

Hyaluronan
Chondroitin sulphate and dermatan sulphate
Heparan sulphate
Keratan sulphate

Question 24

How is Hyaluronan GAG chains created compared to other GAGs chains

Answer 24

Spun out directly from enzyme embedded in plasma membrane

Others are synthesised and attached to core proteins in Endoplasmic Reticulum and Golgi Apparatus in cells

Question 25

Why is Hyaluronan /Hyaluronic acid distinct from other GAGs?

Answer 25

Found in ECM in soft connective tissues. (vitreous humour of eye, synovial joint fluids)

Simply a carb chain without a core protein. Unsulphated.

Can undergo very high amounts of polymerisation, so occupy larger volumes. - up to 25,000 sugars, 10,000 disacharrides - take up a large volume

Question 26

What are the characteristics of Aggrecan?

Answer 26

Cartilage ECM

Highly sulphated GAGs, increasing negative charge and lots of negative carboxyl groups

Large amounts of water in the environment which can resist compressive forces

Question 27

What is the link between ECM and Osteoarthritis?

Answer 27

ECM degradation

With age, aggrecan is cleaved by aggrecanases and metalloproteinases.
Loss of aggrecan to synovial fluid

Question 28

What are Fibrotic diseases due do?

Answer 28

Excessive production of fibrous connective tissue
E.g. Alcoholic liver cirrhosis
Fribrotic lung

Question 29

Extra info

Answer 29

• in fibrillar collagens each ? chain is approximately 1000 amino acids, forming a left handed helix

basement membrane ? surround muscle, peripheral nerve and fat cells, underlie most epithelia. e.g. kidney glomerulus 300nm

• diabetic nephropathy : accumulation of ECM thick membrane - renal failure restricting filtration