Proteoglycans

Question 1

T or F: proteoglycans form a hydrated gel

Answer 1

True

Question 2

What are 2 mainfunctions of proteoglycans?

Answer 2

1. Shock Absorber

2. Joint Lubricator

Question 3

What are the component parts of a proteoglycan?

Answer 3

1. Core Protein

2. Repeating (GAG) disachharide

Question 4

What is a GAG?

Answer 4

• General Name for a disaccharide containing a and acidic sugar to one containing an amino group.

Question 5

T or F: proteoglycans are polycations?

Answer 5

False, they are polyanions

Question 6

What give proteoglycans their cushiony properties?

Answer 6

1. Polyanion GAG segments are attached to a core protein
2. Na+ and H2O bind to the polyanions
3. Na+ and H20 are squeezed out under pressure and are drawn back in when the pressure is removed

Question 7

What type of bond joins glycoaminoglycans (GAGs) to the core protein?

Answer 7

Covalent

Question 8

T or F: the level of hydration of GAGs gives them a large mass relative to their volume.

Answer 8

False, they have a large volume relative to their mass

Question 9

How do proteoglycans use their anionic charge to interact with matrix proteins?

Answer 9

• They find proteins with basic amino acids that are POSITIVELY charged

Sequence:
X-X-B-B-X-B-X

**B= Arginine or Lysine

Question 10

T or F: the inflexible nature of proteoglycans gives them a large volume relative to their mass.

Answer 10

True

Question 11

A large amount of proteoglycans interact with collagen so what can you infer about the charge and residues that must be present in the collagen protein?

Answer 11

1. Positive Residue

2. Has the BBXB sequence where B = Arg or Lys

Question 12

What kind of linkages link GAGs to the core protein of proteoglycans?
- residue?

Answer 12

• O-glycosidic links to Serine

Question 13

What often happens to GAGs to increase their negative charge?

Answer 13

• They are sulfated or Acetylated

Question 14

T or F: a single GAG chain may contain many different types of disaccharide

Answer 14

False, each GAG chain only has ONE type of disaccharide

Question 15

If only a single disaccharide type can be present in each GAG chain, then how can Chondroitin Sulfate and Keratin Sulfate be attached to the same core protein.

Answer 15

• Chondroitin Sulfate and Keratin Sulfate make up PURE GAG chains containing only that disaccharide type
• Different GAG chains can be present on the same core protein as long as each GAG chain is pure

Question 16

What type of GAG is NOT covalently attached to a protein?

• sulfated?
• Where is it found?

Answer 16

Hyaluronate - not associated with a protein
- NOT sulfated

Found in:

• Cartilage
• Vitreous humor

Question 17

What types of GAGs ARE covalently attached to a protein (4 types)?

• type of linkage
• Sulfated?

Answer 17

Types:

1. Chondroitin Sulfate
2. Dermatin Sulfate
3. Heparin
4. Heparin Sulfate

Linkage Type:

• Serine and
• link Xyl-Gal-Gal (trisaccharide)

Sulfated?
- YES

Question 18

Where can you find:

• Chondriotin Sulfate
• Dermatin Sulfate
• Heparin
• Heparin Sulfate

Answer 18

Found in CT and cell surfaces

Question 19

What sequence is needed for O-Glycosylation?

- how does this differ from N-glycosylation?

Answer 19

Asp/Glu - X - Ser - Gly

• The repeat dissacharide GROWs from the Serine rather than a whole group getting transferred from Dolichol

Question 20

What is used to grow the glycosyl chain on GAGs?

Answer 20

UDP-sugars

**Note: these are activated intermediates that cost at least 1 ATP a piece

Question 21

What is PAPS?

Answer 21

Activated sulfate that can be used to make glycoprotein (ATP needs to make PAPS)

Question 22

What links the serine from the ASP/GLU-X-SER-GLY to the GAG?

Answer 22

• A link Trissacharide (e.g. Gal-Gal-Xyl)

Question 23

What links proteins like keratin and collagen to proteins like Aggrecan?

Answer 23

• Link Proteins

NOTE: BXBB sequences are for GAG to core protein, not for collagen to aggrecan

Question 24

What FGF (fibroblast growth factor) a proteoglycan do?

Answer 24

Stores Growth Factors so that they are readily available when they need to be used

Question 25

What is heparin sulfate + growth factor?

Answer 25

Fibroblast Growth Factor

***Important in wound healing etc.

Question 26

Why would you ever want a cell surface proteoglycan (bound in cell membrane) near an integrin protein?

Answer 26

• It can bind integrin protein and make EXTRAcellular proteins like fibronectin compete to bind
• This fine tunes matrix-cell interactions

Question 27

T or F: because of their capacity for making multiple interactions proteoglycans can act as more than just shock absorbers

Answer 27

True, They can interact with Proteins, growth factors, and cells

**All purpose velcro

Question 28

What are the 3 components of aggregating proteoglycans?

Answer 28

1. Proteoglycan Monomers
2. Link Protein
3. Hyaluronate

Question 29

T or F: glycoproteins can act as cell receptors that can bind and cause change within the cell or be internalized along with their ligand

Answer 29

True, these proteoglycans can be integral membrane proteins or they can may be associated through covalent bonds to membrane lipids etc.

Question 30

What is Mucosaccharidosis?

- how is it detected?

Answer 30

• Deficiency in recylcing and degradation of GAG polysaccharids and mucolipids
• Patients accumulate GAG and it is PRESENT IN URINE

Question 31

What are 6 syndromes that result from Mucosaccharidosis?

Answer 31

1. Hunter Syndrome
2. Hurler Syndrome
3. Scheie Syndrome
4. Sanfillipo A, B, C
5. Mucolipidosis VII
6. Tay-Sachs

Question 32

If a proteoglycan core protein is internalized as part of its receptor function what happens to the GAG?

Answer 32

• It is degraded