Fibrillar proteins Flashcards Preview

CMB > Fibrillar proteins > Flashcards

Flashcards in Fibrillar proteins Deck (31):
1

Most abundant protein in the body

Collagen

2

Amino acid composition of type I collagen

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

3

Lysyl hydroxylase

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

4

Prolyl-4-hydroxylase

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

5

Prolyl-3-hydroxylase

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

6

Repeats found in collagen

Gly-Pro-Y and Gly-X-Hyp

7

What is special about collagen amino acid sequence?

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

8

What does one strand of collagen make?

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

9

What do three strands of collagen make?

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.

10

Function of telo-peptides in collagen

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

11

What does lysyl amino oxidase do?

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

12

How do cross-links in collagen form?

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.

13

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

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

14

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

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)

15

Degradation of collagen

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

16

Collagen notation

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

17

Fibrillar collagen types

I, II, III, V, XI

18

Network-forming collagen types

IV

19

Fibril-associated collagen types

IX, XII

20

Type I collagen (need to know)

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

21

Type II collagen (need to know)

Cartilage, vitreous

22

Type III collagen (need to know)

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

23

Scurvy

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.

24

Osteogenesis imperfecta

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)

25

Ehlers-Danlos Syndrome

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.

26

EDS type IV

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

27

EDS type VI

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

28

EDS type VII

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

29

EDS type IX

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

30

Elastin

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).

31

Elastin structure

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