1.14 ECM 2

Question 1

4 major proteins found in the ECM

Answer 1

1. collagen
2. Fibronectin
3. Laminin
4. elastin

Question 2

What are 2 adhesion proteins?

Answer 2

fibronectin and laminin - they attach cells to the extracellular matrix

Question 3

what are the 2 structure proteins?

Answer 3

collagen and elastin - allow stretch and then to return back to original shape

Question 4

What provides the critical link between cells and their surrounding matrix? - attachment point

Answer 4

Integrins mostly attaches to fibronectin

Question 5

What is the most abundant fibrous protein and what does it provide?

Answer 5

Collagen - provides tensile strength, regulates cell adhesion, supports chemotaxis and migration and directs tissue development - transcribed and secreted by fibroblasts into sheets and cables

Question 6

what amino acids are found in collagen?

Answer 6

1. glycine - usually first and every third AA
2. proline
3. hydroxyproline
4. hydroxylysine

Question 7

Is collagen glycosylated?

Answer 7

yes - 3 of the 4 proteins that compose collagen are glycosylated

Question 8

what are the tandem occurrence orders of collagen composition?

Answer 8

Gly-Pro-X
Gly-Y-Hyp
X and Y are any amino acid

Question 9

Why is collagen a poor dietary protein?

Answer 9

It is no where close to using all 20 AA to make a complete protein only a couple make up collagen composition

Question 10

shape of the collagen chain

Answer 10

triple helix -All are constructed from 3 left handed helical peptide chains twisted into a right-handed triple helix - a homotrimer or a heterotrimer - different types of chains yield different types of collagen

Question 11

Type 1 collagen is found where? - majority of collagen is type 1

Answer 11

skin, bone, tendon, blood vessels, cornea

Question 12

Type 2 collagen is found where?

Answer 12

cartilage, intervertebral disk, vitreous body

Question 13

Type 3 collagen is found where?

Answer 13

blood vessels, fetal skin

Question 14

Type 4 collagen is found where?

Answer 14

basement membrane

Question 15

what do collagen molecules all aligned in a staggered fashion and cross linked for strength make?

Answer 15

collagen fibrils

Question 16

Vitamin C is required for?

Answer 16

To hydroxylate proline and lysine

Question 17

Copper is required for?

Answer 17

hydroxylation of lysine

Question 18

Steps 1-9 of collagen synthesis

Answer 18

1. Synthesis of pro-alpha Chain (ER)
2. Hydroxylation of selected prolines and lysines
3. Glycosylation of selected lysines
4. Self-assembly of 3 pro-alpha chains (Golgi)
5. procollagen triple helix formation
6. Secretion in secretory vesicle through plasma membrane
7. Cleavage of propeptides off of procollagen molecule becomes tropocollagen
8. Self-assembly into fibril
9. Aggregation of collagen fibrils into collagen fibers

Question 19

During the cleavage stage of collagen synthesis, what is cleaved off?

Answer 19

the amino and carboxyl terminal groups, this allows the collagen molecules to come together to form the fibril

Question 20

What holds the collagen fibrils together and what enzyme stabilizes it?

Answer 20

covalent crosslinking
lysyl oxidase (LOX) (copper enzyme very reactive makes aldehydes)

Question 21

What 4 requirements are there for collagen fibrillogenesis?

Answer 21

1. fibronectin
2. collagen V
3. integrin alpha2beta1
4. integrin alpha5beta1

Question 22

What type of collagen is non-fibrillar and why?

Answer 22

type IV - lacks regular glycine (small folds prevent tight helix structure)

• nonhelical hindge in the middle - becomes binding site
• molecule is more flexible
• propeptides not cleaved
• bind head to head or tail to tail to form “network”

Question 23

3 steps of collagen degradation

Answer 23

1. enzymes binding
2. unwinding of the triple helix
3. cleavage of collagen peptides

Question 24

What are the 2 enzymes that have the collagenase property to bind and unwind collagen?

Answer 24

1. Matrix metalloproteinases (MMPs)

2. Cathepsins (L and K)

Question 25

What does the initial cleavage yield in collagen degradation?

Answer 25

gelatin - then denaturation and protease digestion followed by phagocytosis

Question 26

What collagen defect has decreased synthesis of type I with long bone fractures/malformed soft bones?

Answer 26

Osteogenesis imperfecta

Question 27

What collagen defect is seen in contortionists and causes translucent skin, easy bruising, and arterial/colon rupture?

Answer 27

Ehlers-Danlos

Question 28

Soluble _________ is secreted into the extracellular space and assembled into elastic fibers (in association with protein FIBRILLIN)

Answer 28

tropoelastin

Question 29

Elastin synthesis is very similar to what?

Answer 29

collagen sysnthesis

Question 30

Elastin is rich in amino acids such as glycine alanine valine proline hydroxyproline and lysine but doesnt have any?

Answer 30

hydroxylysine

Question 31

what 2 conformations are elastin found in?

Answer 31

relaxed and stretched

Question 32

lysyl oxidase allows elastin to make covalent crosslinks called?

Answer 32

desmosine ring - occurs extracellularly and provides stability

Question 33

_________ is a point of attachment for cells and is in the form of a dimer

Answer 33

fibronectin

Question 34

5 things that fibronectin binds

Answer 34

1. integrin 2. collagen 3. fibrin 4. heparan sulfate 5. proteoglycans

Question 35

fibronectin has unique __________ which bind it to integrins

Answer 35

binding sites (amino acids)

Question 36

________is a fibrous and flexible layer that separates organized groups of cells and is secreted by adjacent cells

Answer 36

basal lamina aka tissue divider

Question 37

4 ECM proteins found in all basal laminae

Answer 37

1. laminin 2. perlecan (heparan sulfate PG) 3. type IV collagen 4. entactin/nidogen (glycoprotein)

Question 38

What is the major protein in the basal lamina and its functions

Answer 38

Laminin (cross appearance) -trimeric glycoprotein chains covalently linked by disulfide bonds -short arms =bind to other laminin molecules to make sheets long arms= binding to cells

Question 39

what are integrins?

Answer 39

#1 cell adhesion receptor that is a dimer (usually heterodimer) works as a ligand binding receptor for fibronectin, collagen, fibrinogen, vitronectin