Fibrous proteins

Question 1

Primary amino acid sequence for collagen

Answer 1

Gly-X-Y
X usually proline
Y usually hydroxyproline or hydroxylysinex

Question 2

Fibril-forming collagen types

Answer 2

I, II, and III

tendon, cornea, skin, bone, blood vessels, cartilage, IV discs

Question 3

Network-forming collagen types

Answer 3

IV and VII

basement membrane and beneath stratified squamous epithelia

Question 4

Fibril-associated collagen types

Answer 4

IX and XII

cartilage, tendon, and ligaments

Question 5

Glycosylation of collagen

Answer 5

hydroxyl of hydroxylysine residues enzymatically glycosylated, glucose and galactose sequentially attached

Question 6

Collagen biosynthesis steps

Answer 6

formation of pro-alpha chains (signal sequence cleaved in rough ER) –> hydroxylation in RER–>glycosylation –>assembly of procollagen, formation of disulfide bonds–>vesicular secretion–>extracellular cleavage of procollagen to tropocollagen–>formation of collagen fibrils–>cross-link formation

Question 7

Hydroxylation of collagen requirements

Answer 7

O2, Fe2+, and ascorbic acid (vitamin C)

enzymes: prolyl hydroxylase and lysyl hydroxylase

Question 8

Prolyl hydroxylase and lysyl hydroxylase

Answer 8

enzymes for hydroxylation of collagen precursors

Question 9

N- and C-pro-collagen peptidases

Answer 9

enzymes for extracellular cleavage of terminal propeptides of procollagen to tropocollagen

Question 10

Lysyl oxidase

Answer 10

Cu2+ containing enzyme for covalent cross-linkage of collagen and assembly of elastin
oxidatively deaminates lysyl and hydroxylysyl residues

Question 11

Collagenases

Answer 11

proteolytic enzymes that break down collagen for degradation and remodeling

Question 12

Major collagenopathies (2)

Answer 12

Ehlers-Danlos syndrome (EDS) and osteogenesis imperfecta

Question 13

Ehlers-Danlos syndrome (EDS)

Answer 13

deficiency of collagen-processing enzyme or mutation of collagen
stretchy skin, loose joints, poss. blue sclera
most dangerous: type III collagen defect affecting blood vessels

Question 14

Osteogenesis imperfecta (OI)

Answer 14

decreased production of alpha-1 and alpha-2 chains of collagen
brittle bone syndrome
retarded wound healing and rotated/twisted spine with kyphosis, poss. blue sclera
Type I=OI tarda
Type II=OI congenita, most severe, pulmonary hypoplasia in utero or in infancy

Question 15

Desmosine cross-link

Answer 15

structure of elastin
allows for stretching of molecule
= 3 allysyl (oxidatively deaminated) side chains +1 lysyl side chain

Question 16

Fibrillin

Answer 16

scaffold for tropoelastin assembly into elastin

Question 17

Marfan syndrome

Answer 17

mutation in fibrillin-1 protein
inhibited formation of functional microfibrils because of abnormal fibrillins
connective tissue disorder of skeleton, eyes, and cardiovascular system, skeletal abrnormalities, heart defects, scoliosis, poss. blue sclera

Question 18

Alpha-1-antitrypsin deficient emphysema

Answer 18

defects in alpha-1-AT prevent its normal inhibition of elastase, allowing elastase to destroy connective tissue of alveolar walls and lead to emphysema
polymerization of alpha-1-AT in liver may lead to cirrhosis
homozygotes for gene only show disease

Question 19

Alpha-1-antitrypsin

Answer 19

inhibits proteases incl. neutrophil elastase, a protease that degrades elastin of alveolar walls
released by liver, monocytes, and alveolar macrophages

Question 20

Scurvy

Answer 20

deficiency of ascorbic acid (vitamin C)
lack of reducing agent leads to non-functional hydroxylating enzymes of procollagen, leading to impaired collagen helix formation and cross-linkage
symptomatic weakness, anemia, gum disease, and limb bruising due to capillary fragility