Proteins IV

Question 1

What is the secondary structural unit in collagen?

Answer 1

Polyproline Type II-like helix

Question 2

Which Ehlers-Danlos Syndrome (EDS) is associated with a type I collagen mutation.

Answer 2

Arthrochalasis

Question 3

What two fibrous proteins exist as dimers (and rarely trimers) of right-handed alpha helical chains?

Answer 3

alpha-Keratin and tropomyosin

Question 4

How are alpha-keratin and tropomyosin arranged around each other?

Answer 4

parallel and coil about each other in a left-handed super twist

Question 5

What protein is appropriate for hydrophobic packing to stabilize the force for the tropocollagen helix?

Answer 5

Glycine (its the only aa small enough)

Question 6

ALL collagen has an extensive, repeated tripeptide sequence “Gly-X-Y”. What are “X” and “Y” usually?

Answer 6

Proline and Hydroxyproline respectively

Question 7

Kyphoscoliosis EDS is due to a mutation in the gene for

Answer 7

Lysyl Hydroxylase

Question 8

What is the functional unit of collagen?

Answer 8

Tropocollagen

Question 9

How are individual collagen polypeptide chains in tropocollagen stabilized?

Answer 9

Via H-bonds between the amino terminus-glycine residue and the carboxy terminus-proline (or hydroxyproline) residue.

Question 10

What dictates the antigen Ig will bind to?

Answer 10

The Hyper-variable Regions (Complementarity Determining Regions) on the heavy and light variable chains of Immunoglobulins.

Question 11

What is the collagen content (percentage) in the skin?

Where in the body is collagen content the lowest?

Answer 11

• 74%

- liver (4%)

Question 12

Osteogenesis imperfecta is an autosomal dominant disorder associated with what type of collagen mutation? What gene location does this occur at?

Answer 12

• Type I collagen

- alpha (I) chain

Question 13

What enzymatic process must occur to prevent vessels, skin, and tendons from becoming fragile?

Answer 13

Hydroxylation of proline in procollagen formation

Question 14

In the formation of collagen, what molecules are organized into bundles called fibrils? What occurs following this collagen formation step?

Answer 14

• Tropocollagen

- cross-linkage to form fibers

Question 15

What individual regions are created by the cleavage done by papain?

Answer 15

2 Fab (antigen-binding fragment) and 1 Fc (fragment crystallization)

Question 16

What region of papain does cleavage take place at?

Answer 16

The hinge region (between CH1 and CH2 of both heavy chains)

*CH = Constant Heavy chain

Question 17

What is the fundamental tertiary structural element of antibodies?

Answer 17

The Ig Fold

Question 18

What region of an antibody participates in antigen-binding?

Answer 18

The loops containing HVR/CDRs

Question 19

During fibrillar collagen formation, what oligosaccharide-linked amino acid is added to the C-terminal of procollagen?

Answer 19

Asparagine (Asn)

Question 20

Aggregation of antigens is possible due to what two factors?

Answer 20

1) Antigens posses multiple antigenic determining reasons

2) Antibody bivalency

Question 21

Name the key modification products of Lysine/hydroxylysine residues

Answer 21

1) Allysine
2) Hydroxyallysine
3) Lysinorleucine
4) Aldol Crosslink

Question 22

What is the key enzyme (and its cofactor) involved in tropocollagen fibril cross-linking?

Answer 22

• Lysyl-amino oxidase

- Cu2+

Question 23

What gives fibrils a striated appearance in an electron micrograph?

Answer 23

The 67 nanometer staggering of trimers

Question 24

What are the components of the basal lamina?

Answer 24

The collagen layer:

• type IV collagen
• Nidogen/entactin

The Laminin layer:

• laminin
• perlecan

Question 25

What syndrome is caused by faulty synthesis of collagen?

Answer 25

Ehler's-Danlos Syndrome (EDS)

Question 26

Name the 6 major types of Ehler's-Danlos Syndrome?

Answer 26

``` Type 1 - Hyper-mobility Type 2 - Classic Typer 3 - Vascular Type 4 - Arthrochalasis Type 5 - Kyphoscoliosis Type 6 - Dermatosparaxis ```

Question 27

Where is the hydrophobic stripe formed between alpha-keratin and tropomyosin? What is the purpose of this stripe formation?

Answer 27

- Between residues "a" and "d" in the a-g heptad | - Stabilizes the coil-coiled structure

Question 28

Where do interchain salt bridges form between alpha-keratin and tropomyosin?

Answer 28

- Between residues "e" and "g" | * these should be charged aa's

Question 29

What fibrous proteins have the possibility of forming both homo and hetero-dimers and trimers?

Answer 29

Alpha-keratin and tropomyosin

Question 30

Compare and contrast the residues/turn and pitch of an alpha helix vs a polyproline type II helix, as well as its coil structure.

Answer 30

3.3 residues/turn (3.6 for α-helix) 9.4 Å pitch (5.4 Å for α-helix) Left-handed coil (α-helix is usually right-handed)

Question 31

In the hydroxylation of proline, what cofactors are required for prolyl hydroxylase function?

Answer 31

- Ascorbate (Vit C) | - Fe2+

Question 32

What collagen type are the basement membrane and lens capsule composed of?

Answer 32

Type IV

Question 33

Type IV collagen only contains small amounts of which two amino acids?

Answer 33

Alanine (Ala, A) and Arginine (Arg, R)

Question 34

What percent carbohydrate content is type IV collagen?

Answer 34

15%

Question 35

Good Pasture's syndrome is a hypersensitivity reaction to antigens in the non-collagenous domain of what collagen type/chain gene?

Answer 35

Type IV/alpha(3) chain

Question 36

What organs does Good Pasture's Syndrome affect?

Answer 36

The glomerulus and pulmonary alveoli

Question 37

What is the purpose of the frequently appearing proline and hydroxyprolines in the polyproline structure?

Answer 37

Minimization of steric clash between pyrrolidine side-chain and peptide backbone.

Question 38

What may cause Hypermobility (Type 1) EDS

Answer 38

- joint dislocation - type III collagen mutation - tenascin-X mutation

Question 39

Which EDS is the most rare and what is its mutation?

Answer 39

Vascular (type III)

Question 40

How many loops define an antigen binding site?

Answer 40

-6

Question 41

How many antigen binding sites are there per Ig fold?

Answer 41

-3

Question 42

Which fibrous protein is abundant in ligaments, the lungs, and skin?

Answer 42

Elastin

Question 43

What lysine modification does elastin form crosslinks with?

Answer 43

Allysine

Question 44

Which chaperone protein binds to helices in collagen and what is the outcome of this binding?

Answer 44

- Hsp47 (Heat Shock Protein) | - prevents premature aggregation

Question 45

What reaction do Nitrogen and Carbon proteinases (Bone Morphogenic protein) catalyze?

Answer 45

The removal of N & C terminal propeptides