Collagen/Elastin

Question 1

Tri-peptide repeat in collagen

Answer 1

Gly-X-Y

X = proline
Y = hydroxyproline

Question 2

How does hydroxylation of proline stabilize the collagen helix?

Answer 2

It ‘fixes’ the side chain of the proline into the exo confirmation

This confirmation is preferred in the Y position

This increases the collagen’s thermal stability and keeps it from unwinding and getting degraded

Question 3

Mutation is which residue will cause a disease state in the triple helix and why?

Answer 3

Glycine…it has a Hydrogen R-group…any other bigger side chain will disrupt the tight packing of the triple helix

This will make the helix susceptible to degradation

Question 4

Post-translation modifications of collagen…inside the cell

Answer 4

1. Hydroxylation of proline and lysine residues in the polypeptide
2. Gylcosylation of hydroxylysine residues
3. Disulfide bond formation at C-terminal propeptide extension

Question 5

Vitamin that is needed for proper collagen fibril formation?

Answer 5

Vitamin C

It is a cofactor to the enzyme…

Required for prolyl and lysyl hydroxylation

Question 6

Post-translation modifications of collagen after molecule has been secreted?

Answer 6

1. N & C terminal extensions are clipped from the procollagen molecule…done by peptidases
2. Lysyl oxidation

Question 7

Why are post-translation modifications separated by inside/outside of the cell?

Answer 7

Prevent tropocollagen molecule from self-assembling inside the cell

Question 8

Diseases from improper post-translation modifications of collagen?

Answer 8

Ehlers-Danlos Syndrome —> deficiency of procollagen peptidases

Menke’s Syndrome —> defect in cupper (Cu2+) absorption or metabolism…which is needed as a cofactor for the enzyme responsible for crosslinking collagen fibrils outside the cell (lysyl oxidase)

Question 9

Major collagen in bone

Answer 9

Type I

Question 10

Major collagen in basement membranes?

Answer 10

Type IV

Question 11

Relation between type IV collagen and hereditary nephritis?

Answer 11

The double basement membrane in the glomerulus is responsible for keeping proteins in the plasma from spilling to the urine during glomerular filtration

Question 12

Cause of emphysema?

Answer 12

Increased degradation of elastin in the lung

Question 13

What is fibrillin?

What disease is associated with mutations in the fibrillin gene?

Answer 13

Fibrillin is a glycoprotein that coats elastin fibers

Marfan’s syndrome

Question 14

Elastin

Answer 14

Highly hydrophobic protein rich in glycine and proline

Repeats of Val-Pro-Gly-Val-Gly

Secondary structure = random coil that can stretch and relax

Desmosine and isodesmosine = the crosslinks that help elastin return to its original conformation

Question 15

Alpha1 - antitrypsin

Answer 15

Produced in liver

Prevents elastin degradation by inhibiting elastase activity

Deficiency = can cause emphysema and cirrhosis of the liver

Smoking can also stimulate the activity of elastase to levels that cannot be controlled by alpha1-AT

Question 16

Marfan’s Syndrome

Answer 16

NO osteoporosis

Mental retardation and thrombosis are UNCOMMON

Autosomal dominant

Lens DISLOCATE UP

No approved treatments

Question 17

Homocystinuria

Answer 17

Frequently have osteoporosis

Mental retardation and thrombosis COMMON

Autosomal recessive

Lens dislocate DOWN

Can be treated with dietary supplements

Question 18

Osteogenesis imperfecta

Answer 18

Symptoms: fragile bones that fracture easily…blue sclera…triangular faces…loose joints….brittle teeth

Cause: Malfunction in the body’s production of collagen

Type I: most common, blue sclera, and hearing loss, autosomal dominant…normal stature and little to no deformity

Type II: lethal in the perinatal period…structural alterations in both chains of collagen and is autosomal dominant

Question 19

Bisphosphonates

What are they used to treat?

Answer 19

Used to treat osteogenesis imperfecta

Act by inactivating osteoclasts

Some can also decrease the apoptosis of osteoblasts

Question 20

Tropocollagen

Answer 20

Type I collagen triple helix

Question 21

How are the chains of the triple helix are stabilized

Answer 21

Interchain H-Bonds

Question 22

Proline preferred conformation

Answer 22

Endo-

(Hydroxyproline = exo)

Most thermodynamically stable for both…

Question 23

Proline-4-hydroxylase

Answer 23

Uses vitamin C as a cofactor

Responsible for post-translation modifications of proline and hydroxyproline

Question 24

Purpose of the disulfide bond formation in the post-translation modifications of collagen?

Answer 24

Needed to initiate the triple helix formation…brings the strands close together

Question 25

What happens once the C & N terminals of the procollagen molecule are cleaved outside the cell in the ECM?

Answer 25

The collagen fibrils can self-assemble through cross-linking

Question 26

Lysyl oxidase

Answer 26

Responsible for cross-linking the collagen molecule into fibrils in the ECM

Needs Cu2+ as a cofactor

Question 27

Type II collagen

Answer 27

Found in cartilage and vitreous humor

Question 28

Type III collagen

Answer 28

Extensive connective tissue (skin, lungs, blood vessels)

Question 29

Type VII collagen

Answer 29

Anchoring filament, forms attachments of basal laminae to underlying connective tissue

Clinical: defect = Epidermolysis bullosa

Question 30

Alport Syndrome (hereditary nephritis)

Answer 30

Results from mutated Type IV collagen

Messes up the basement membrane of the glomerulus