Extracellular Matrix Proteins

Question 1

Types I to IV account for what % of human collagen?

Answer 1

Over 90%

Question 2

What are the tissues associated with collagens type I through IV?

Answer 2

I: Major component of Skin and Bone (also tendons)

II: Primarily in Cartilage

III: Found in blood vessels. Key role in wound healing

IV: Basement membrane of cells “basal lamina”

Mneumonic: SCVB: South Carolina Vetoed Bands

Question 3

All collagens contain __ polypeptide chains. And all collagens have at least one ___.

Answer 3

3; triple helix domain

Question 4

1. Which 3 collagens have common structural characteristics?
2. Each of these 3 collagen polypeptide chains has ~ ___ AA’s,
3. each individual chain is called ___.
4. Mature collagen of these has ___ ____.
5. Every 3rd AA is collagen is ___.
6. Collagen contains about 20%___ and ___.
7. Collagen contains about __% hydroxylysine.

Answer 4

1. Collagens I, II, III
2. 1000
3. alpha chain
4. 3 alpha chains
5. Glycine
6. Proline;hydroxyproline
7. 1-5%

Question 5

Name 4 ways the collagen helix is VERY DIFFERENT from the alpha helix.

Answer 5

1. It is more extended than an alpha helix
2. It doesn’t have intrachain H bonds
3. It’s stablized by steric repulsion of pyrrolidone rings
4. The collagen helix is essentically a tertiary structure

Question 6

1. The collagen triple helix is rod-shaped. How long and wide is it?
2. How are the 3 collagen strands bonded to each other?
3. What else participates in interchain H bonds to further stabilize the triple helix?

Answer 6

1. 3000 Angstroms long, 15 Angstroms wide.
2. The strands are hydrogen bonded to each other via NH of glycine residue and CO of other residues.
3. Hydroxyproline.

Question 7

What is needed for hydroxylation of proline and lysine?

Answer 7

Ascorbic acid (aka vitamin C)

Question 8

Hydroxylated ___ residues provide sites for ____.

Answer 8

Lysine; Glycosylation

Question 9

What is the basic process for making mature collagen?

Answer 9

Translation will lead to procollagen formation, which is secreted and processed to form tropocollagen, which is then packed to form a collagen fibril, packed and stacked some more to form mature collagen.

Question 10

How are collagen fibrils crosslinked?

Answer 10

Extracellular enzyme Lysyl Oxidase initiates crosslinking by forming aldehyde derivatives of lysine and hydroxylysine.

Question 11

What even in sythensis of fibrous collagen happens just before the procollagen is secreted?

Answer 11

The triple helix of the 3 collagen strands are folded.

Question 12

Cross linking involves nonenzymatic rxns b/w which 2 groups?

Answer 12

lysyl and allysl groups.

Question 13

Where is Elastin found? Elastin is synthesized as what kind of precursor?

What is special about elastin?

Answer 13

It is found in elastic fibers of the ECM, and in elastic tissue like smooth muscle and lung. It is synthesized as a highly soluble tropoelastin precursor.

It has alternating hydrophilic and hydrophobic domains which contribute to its functional elasticity

Question 14

Where does laminin bind to and crosslink other proteins?

Answer 14

In the basal laminae.

Question 15

Laminin is ____ with ____ subunits.

These subunits form a ____ association domain.

Answer 15

heterotrimeric with alpha, beta, and gamma subunits.

They form a triple helix association domain.

Question 16

What is special about the N-termini and C-termini of the subunits in laminin?

What is the function of this?

Answer 16

The triple helix association domain composing of 3 subunits all have N-terminal globular extensions, while only the alpha subunit has an additional C-terminal globular domain.

The globular domains interact w/ other cell surface proteins and conect the basal laminae to the cell.

Question 17

What is a proteoglycan?

Answer 17

It is a polypeptide chain w/ lots of covalently bound polysaccharides.

NOTE: Polysaccharides make up 95% of of weight. They also provide a negative charge (they may be sulfated and carboxylated)

Question 18

What do proteoglycans form?

Answer 18

They form a gel, which provides mechanical support, and allows diffusion of SMALL MOLECULES.

The gell has ECM proteins embedded in it.

Question 19

What are the long unbranched polysaccharides of proteoglycans called?

Answer 19

Glycosaminoglycans (GAGs), composed of repeating disaccharide units that are frequently sulfated.

Question 20

How is the GAG usually attached to the protein?

Where does glycosylation occur?

Answer 20

Via a Ser or Thr residue attached to a trisaccharide linker.

In the ER

Question 21

Integrins are the major membrane protein that link cells to the ECM. What proteins do they attach to?

What is the structure of integrin protein?

Answer 21

Adehsion proteins like fibronectins;

Integrins are a dimer of alpha and beta subunits.

Question 22

What can activation of integrin proteins cause?

Answer 22

Cell adhesion and cell migration (important for cancer)

Question 23

Deficiency of vitamin C will cause____.

Answer 23

Scurvy