Lecture #10 - Collagen And The Ecm

Front 1

What are the 4 components of the ECM?

Back 1

Collagen
Glycoaminoglycans + Proteoglycans
Fibronectin
Elastin and elastic fibers

Front 2

What are the 3 main functions of the ECM?

Back 2

active component of tissue
regulates behavior of cells
determines physical properties of tissues

Front 3

What are the two major types and what do they consist of?

Back 3

Fibrillar collagen -Type I
Type I is most abundant - Found in skin, teeth, bones
Type II - cartilage
Type III - same as type I
Non-Fibrillar Collagens

Front 4

Some collagens are considered homotrimers while others are considered heterotrimers. What does this mean?

Back 4

Collagen is unique in its structural triple helix
Homotrimers - all 3 chains coded for by one gene (Type III)
Heterotrimers - 3 chains coded for by multiple genes (Type I)

Front 5

Describe the biosynthesis of collagen.

Back 5

Translated as pro-collagen
Hydroxylated and Glycosylated
Trimer forms/secreted from cell
Pro-peptides removed
Triple helices assemble into fibrils
Non-fibrillary collagen does not

Front 6

What is the so-called unusual structure of collagen?

Back 6

It is three left-handed chains that form a trimer that makes a right handed triple helix

Front 7

What stabilizes this structure?

Back 7

Hydrophobic forces

Front 8

What creates this unique structure?

Back 8

It is a reflection of a unique amino acid composition.
Gly-X-Y where X and Y are usually proline and hydroxyproline

Front 9

Hydroxylation is essential for collagen folding?
What is the enzyme that catalyzes the hydroxylation of collagen?

Back 9

prolyl hydroxylase

Front 10

What is the cofactor needed?

Back 10

ascorbate

Front 11

Besides hydrophobic interaction, what else stabilizes the helix?

Back 11

Hydroxyproline residues via hydrogen bonding

Front 12

Besides proline and hydroxyproline, what is the other amino acid seen in collagen residues?

Back 12

Hydroxylysine

Front 13

What is the function of this hydroxylysine site?

Back 13

It provides sites for glycosylation which decreases the diameter of the fibril

Front 14

What is this hydroxylation catalyzed by?

Back 14

Lysyl hydroxylase
Cofactor is ascorbate and Fe

Front 15

The unique Gly-X-Y repeats result in a triple helix in which only Gly can fit int he center of the helix. What is the significance of this?

Back 15

Any other amino acid would destabilize the helix and the collagen would melt prematurely.

Front 16

What is the cause of the osteogenesis imperfecta?

Back 16

A mutation in the collagen chain where a substitution in aa causes destabilization of the collagen.

Front 17

Triple helices are cross-linked in a staggered formation to form fibrils. What is the enzyme that catalyzes this cross linking?

Back 17

Lysyl oxidase
Occurs between lysyl residues

Front 18

What is a key difference in self assembly between fibrillary and non-fibrillary collagen molecules?

Back 18

In fibrillary collagen helices, the pro-peptide is cleaved after being secreted into the ECM.
In non-fibrillary collagen helices, the pro-peptide is retained.

Front 19

What is the difference between fibrillary and non-fibrillary collagen helices in terms of post-translational modifications?

Back 19

Fibrillary collagen helices are O-glycosylated
Non-fibrillary collagen helices are N-glycosylated and have glycoaminoglycans attached to them.

Front 20

What are glycoaminoglycans?

Back 20

Unbranched polysaccharide chains composed of disaccharide repeats.
They are highly negative.

Front 21

What is a major function of glycoaminoglycans?

Back 21

They are hydrophilic and function to suck water into the ECM.
They enable the ECM to withstand compressive forces and are especially useful in the cartilage.
ex. the knee can support very high pressures.

Front 22

What are the 4 components of Glycoaminoglycan's?

Back 22

Hyaluronan
Chondroitin sulfate and dermatan sulfate
Keratin sulfate
Heparan sulfate

Front 23

Hyaluronan is the prototypical GAG. What is its primary function?

Back 23

As a space filler during development to allow space during cell migration into new organs.

Front 24

Once cell migration occurs, what enzyme breaks down hyaluronan?

Back 24

Hyaluronidase

Front 25

How is hyaluronan used therapeutically?

Back 25

It is an important component of joint fluid and is used to treat osteoarthritis.

Front 26

What are proteoglycans?

Back 26

GAGs joined to a protein core

Front 27

How is the GAG linked to the protein?

Back 27

By a link tetrasaccharide

Front 28

What is an aggrecan? decorin?

Back 28

aggrecan = proteoglycan with over 100 GAG chains
decorin = proteoglycan with just 1 GAG chain

Front 29

What are function of proteoglycans?

Back 29

Provide hydrated space between cells.
Bind to other secreted proteins to regulate the activities of the ECM
Some can act as co-receptors on the cell surface

Front 30

What is fibronectin?

Back 30

A large glycoprotein composed of 2 subunits.

Front 31

What is the function of the fibronectin?

Back 31

Helps cells attach to the ECM - adhesion

Fibronectin contains modular domains that are found in many of the proteins with which fibronectin interacts

Front 32

There are several isoforms of fibronectin due to alternative splicing. What are the two major isoforms?

Back 32

Plasma - soluble and found in blood and bodily fluids. Important in wound healing
Cellular - forms fibrils on cell surface that are highly disulfide bond crosslinked.

Front 33

What directs the formation of these fibrils?

Back 33

Intracellular actin filaments
Mediated by Integrins

Front 34

What is Ehlers Danlos syndrome?

Back 34

A platelet aggregation disorder in which a deficiency in the plasma isoform of fibronectin. This isoform of fibronectin is crucial for platelet aggregation.

Front 35

What type of tissue contains elastin, elastic fibers or microfibrils?

Back 35

In tissue that requires a great deal of resilience. Tissue that recoils after a transient stretch (ligament or tendon...not achilles tendon)

Front 36

As with collagen, elastin is cross linked by a certain enzyme. What is this enzyme?

Back 36

Lysyl oxidase

Front 37

The elastin core is covered with a sheath of ....

Back 37

Microfibrils

Front 38

What is the major component of microfibrils?

Back 38

Fibrillin

Front 39

What is caused by mutations in fibrillin?

Back 39

Marfan syndrome

Front 40

What is a major function of microfibrils?

Back 40

They are the scaffold upon which elastic fibers are assembled. They are then displaced to the periphery of the growing elastin fiber