Fibrillar proteins

Question 1

Most abundant protein in the body

Answer 1

Collagen

Question 2

Amino acid composition of type I collagen

Answer 2

33% Gly, 10-13% Pro, 10% hydroxyproline (OH-Pro, Hyp), 1% hydroxylysine (OH-Lys)

Question 3

Lysyl hydroxylase

Answer 3

Hydroxylates lysines in X-Lys-Gly to 5-OH-Lys. Requires Fe2+, oxygen, _-ketoglutarate, and ascorbic acid (Vitamin C).

Question 4

Prolyl-4-hydroxylase

Answer 4

Converts prolines in X-Pro-Gly to 4-OH-Pro. Requires Fe2+, oxygen, _-ketoglutarate, and ascorbic acid (Vitamin C).

Question 5

Prolyl-3-hydroxylase

Answer 5

Hydroxylates prolines in Hyp-Pro-Gly to 3-OH-Pro. Requires Fe2+, oxygen, _-ketoglutarate, and ascorbic acid (Vitamin C).

Question 6

Repeats found in collagen

Answer 6

Gly-Pro-Y and Gly-X-Hyp

Question 7

What is special about collagen amino acid sequence?

Answer 7

1. Gly is smallest AA, will fit into small places in the core of structure 2. Pro is a helix-breaker so regular _-helix cannot form 3. Hydroxyl group can react to form crosslinks (the more Hyp residues the stronger the triple-helix) and allow O-linkage for sugars

Question 8

What does one strand of collagen make?

Answer 8

Polyproline type II helix: loose, left-handed helix. Plane of each peptide bond is perpendicular to the axis of the helix.

Question 9

What do three strands of collagen make?

Answer 9

Three-member superhelix: right-handed triple helix. Each strand is labeled an _-chain. Peptide carbonyl groups form strong interchain H-bonds with other collagen chains.

Question 10

Function of telo-peptides in collagen

Answer 10

N and C terminal segments are the sites for cross-linking.

Question 11

What does lysyl amino oxidase do?

Answer 11

Copper-dependent ezyme that converts Lys epsilon amino groups to aldehydes to form allysine

Question 12

How do cross-links in collagen form?

Answer 12

Lysyl amino oxidase uses copper to convert Lys epsilon amino groups to aldehydes to form allysine. The aldehydes spontaneously react with non-modified Lys epsilon groups (or with aldehydes from other allysines) to form covalent bond cross-links.

Question 13

Steps to biosynthesis of collagen-inside the cell (8 steps)

Answer 13

1. Translation of 3 _-chains on ribosomes along RER-called preprocollagen (pre- directs chain to ER and pro- means terminal residues that direct assembly and get taken off later) 2. Peptide chains sent to lumen of RER 3. “Signal peptidase” cleaves signal peptides to make procollagen 4. Hydroxylation of lysine and proline inside lumen of ER by respective enzymes 5. Glycosylation of specific hydroxylysine residues for stablilzation 6. Intra and inter chain disulfide bond formation facilitating triple helix formation 7. Triple helical structure formed in RER 8. Procollagen shipped to golgi apparatus for glycosylation completion and secretion via exocytosis

Question 14

Steps to biosynthesis of collagen-outside the cell (3 steps)

Answer 14

1. Upon secretion propeptides (registration peptides) cleaved by procollagen peptidases to make tropocollagen 2. Multiple tropocollagen molecules self-assemble into collagen fibrils and multiple fibrils form into collagen fibers (the quarter-staggered configuration)

Question 15

Degradation of collagen

Answer 15

Metalloproteinases (MMPs) called collagenases catalyze hydrolysis of collagen. Once clipped by collagenase the triple helix unwinds and gets futher degraded by Gelatinases (also MMPs)

Question 16

Collagen notation

Answer 16

[_1(I)]2_2(I) _1 and _2 denotes the two chains, I means type I collagen

Question 17

Fibrillar collagen types

Answer 17

I, II, III, V, XI

Question 18

Network-forming collagen types

Answer 18

IV

Question 19

Fibril-associated collagen types

Answer 19

IX, XII

Question 20

Type I collagen (need to know)

Answer 20

Bone, skin, tendon, scar tissue, heart valve, intestinal, and uterine wall

Question 21

Type II collagen (need to know)

Answer 21

Cartilage, vitreous

Question 22

Type III collagen (need to know)

Answer 22

Blood vessels, newborn skin, scar tissue, intestinal, uterine wall

Question 23

Scurvy

Answer 23

Ascorbic acid (vitamin C) deficiency. Since ascorbic acid is necessary for collagen formation, causes abnormal bone development/repair, osteoporosis, fragile capillaries, loosening of teeth, swollen bleeding gums, poor wound healing.

Question 24

Osteogenesis imperfecta

Answer 24

Genetic collagen disorder, brittle bone disease. Multiple types depending on the specific mutation. Mutation in either the _(I) or _(II) genes for type I collagen result in abberant _-chains. Unstable collagen or truncated chains form that are rapidly degraded. GLY SUBSTITUTIONS lead to the MOST SEVERE forms of disease. Characterized by multiple fractures, bone deformities, progressive deafness, blue sclera (blue-grey color in eyes), defective dentition (poor teeth)

Question 25

Ehlers-Danlos Syndrome

Answer 25

Group of disorders leading to weakened connective tissues. Could be many different gene deficiencies. Symptoms include fragile skin, impaired joint mechanics, hyper-extensibility of skin, hyper-mobility of joints.

Question 26

EDS type IV

Answer 26

Autosomal dominant mutation causing deficiency in type III collagen formation. Thin skin, easily ruptured arteries and internal viscera.

Question 27

EDS type VI

Answer 27

Autosomal recessive deficiency in lysyl hydroxylase. Scoliosis, velvety skin, hypermobile joints, tendency towards ocular injuries.

Question 28

EDS type VII

Answer 28

Autosomal dominant mutation that leads to an inability to remove the N-terminal polypeptide. Hypermobile joints, prone to dislocations, soft skin.

Question 29

EDS type IX

Answer 29

X-linked recessive deficiency in lysyl oxidase (or copper deficiency) that results in decreased cross-linking. Hyperextensible skin, bladder diverticulae, skeletal deformities.

Question 30

Elastin

Answer 30

Provides elasticity to tissues. Fibrous, apolar, relatively insoluble. Lacks regular secondary structure, but contains unordered coiled structure where AA highly mobile. Contain allysines (modified lysine residues).

Question 31

Elastin structure

Answer 31

Thee allysines and one unmodified lysine react to form heterocyclic structure of desmosine and isodesmosine. Desmosines covalently cross-link chains in elastin.