Collagen

Question 1

What tri-peptide is found as a regular repeat in fibril-forming collagens?

Answer 1

Gly-X-Y

X=proline

Y=hydroxyproline

Question 2

Why does hydroxylation of proline stabilize the collagen helix?

Answer 2

Hydroxylation of proline fixes the side chain in the exo conformation, whicih is preferred for proline sidechains in the Y position –> increases collagen’s thermal stability & prevents unwinding

Question 3

Why does collagen have such high tensile strength?

Answer 3

Multiple interchain hydrogen bonds and dense packing of the triple helix

Question 4

Mutation of what residue in collagen would be most likely to cause disease and why?

Answer 4

Glycine

Any sidechain other than the hydrogen of Gly would disrupt packing in the collagen triple helix

Question 5

Post translational modifications of collagen that occur inside the cell

Answer 5

Hydroxylation of Pro & Lys

Glycosylation of hydroxylysine

Disulfide bond formation at C-terminal propeptide extension

Question 6

Why is vitamin C required for proper collagen fibril formation?

Answer 6

It’s required for prolyl and lysyl hydroxylation, which stabilizes the triple helix

Question 7

What post-translational modifications of collagen occur after the molecule has been secreted?

Answer 7

Peptidases clip off N- and C-terminal extensions from the procollagen

Lysyl oxidation

Question 8

Why do some modifications occur inside the cell and some outside?

Answer 8

Prevents the tropocollagen molecule from self-assembling inside the cell

Question 9

Ehlers-Danlos syndrome

Answer 9

Deficiency in procollagen peptidase

–> carboxyl- and amino-terminal ends of procollagen aren’t cleaved into tropocollagen in the ECM, so fibrils don’t form

–> loose joints

Question 10

Menke’s syndrome

Answer 10

Defect in copper (Cu) absorption or metabolism–> kinky, steel-colored hair, growth retardation, neural issues

Lysyl oxidase requires Cu2+ as a cofactor to crosslink collagen fibrils

Question 11

Major collagen type in bones

Answer 11

Type I

Question 12

Major collagen type in basement membranes

Answer 12

type IV

Question 13

Why do disorders in type IV collagen cause hereditary nephritis?

Answer 13

Type IV collagen is the major scaffold protein of the basement membrane.

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

Question 14

Increased degradation of elastin in the lung causes

Answer 14

emphysema

Question 15

Fibrillin

Answer 15

Glycoprotein that coats elastin fibers

Question 16

Marfan’s syndrome is a genetic disease that involves mutations in

Answer 16

The fibrillin gene

Question 17

Elastin- what composition gives it its characteristic properties?

Answer 17

Highly hydrophobic protein rich in Gly and Pro; repeating peptapeptide Val-Pro-Gly-Val-Gly

Unique cross-links (desmosine & isodesmosine) allow it return to its original conformation

Question 18

Secondary structure of elastin

Answer 18

Random coil that can stretch and relax

Question 19

Elastic fibrisl are covered with

Answer 19

Microfibrils composed primarily of the glycoprotein fibrillin

Question 20

a1-Antitrypsin

Answer 20

Produced primarily in the liver

Prevents elastin degradation by inhibiting elastase

Question 21

A deficiency of a1-AT can cause

Answer 21

Emphysema and cirrhosis of the liver

(cigarette smoek can also stimulate elastase to lvls that can’ tbe controlled by a1-AT)

Question 22

Big differences between Marfan’s and Homocystinuria

Answer 22

Question 23

Fragile bones that break easily, triangular-shaped face, blue sclera, hearing loss, scoliosis, thin, smooth skin, loose joints, low muscle tone, brittle teeth

Answer 23

Type I Osteogenesis Imperfecta - AD mutation that reduces type I collagen by 50%

Question 24

Type II OI

Answer 24

Type II is more severe, resulting in death during embryogenesis or by bone fracturing during birthing; results from a change in the modifications that occur to collagen during synthesis

Question 26

Treatment of osteogenesis imperfecta

Answer 26

**Bisphosphonates** inactivates/causes apoptosis of osteoclasts (breaks down bone tissue) and decreases apoptosis among osteoblasts (lays down new bone)

Question 27

Tropocollagen

Answer 27

The triple helix of type I collagen

Question 28

Tendon vs skin Collagen & elastin content

Answer 28

Tendon needs to be strong -\> collagen Skin needs to stretch -\> elastin

Question 29

Scurvy

Answer 29

Deficiency of vitamin C --\> **proline-4-hydroxylase** can't convert Pro to 4-hydroxypro for the Y position in collagen --\> unstable collagen --\> weakness, spongy/bleeding gums, poor wound healing, follicular hyperkeratosis, perifollicular hemorrhage

Question 30

Fibril collagens

Answer 30

Types 1, 2, 3, 5, 11 Characteristic tropocollagen tripl ehelix that forms staggered fibrils --\> striation

Question 31

Collagen synthesis

Answer 31

1. Translation on RER into **preprocollagen** 2. Translocation into the ER while **p****roline 4-hydroxylase** generates 4-hydroxyprolines at the Y position 3. Cleave off signal sequence & form a triple helix in the cytosol into **procollagen** 1. ​Disulfide bonds between carboxyl-terminal ends 4. Secretion out into the ECM, where **procollagen peptidases** cleave the carboxyl-terminal and amino-termianl ends into **collagen**

Question 32

Fibril-associated collagens

Answer 32

Interrupted triple helcies with globular heads on them

Question 33

Sheet/network-like collagen

Answer 33

type 4 inthe basement membranes and basal lamina

Question 34

Anchoring fibrils

Answer 34

type 7 Supports or connects dermal and epidermal layers

Question 35

Alport's syndrome

Answer 35

Disorders of **basement membranes of kidney, cochlea, and eye** due to mutations in **type 4** **collagen** in basement membranes & basal lamina. --\> **proteinuria, HTN, end-stage renal disease, hearing loss** **X-linked or AD**, depending on which type IV collagen gene is involved