Lecture 5

Question 1

What is the general structure of of glycosaminoglycans (GAGs)?

Answer 1

Carbohydrates composed of repeating disaccharide units

Question 2

Give 4 examples of GAGs?

Answer 2

1. Chondroitin Sulphate (CS)
2. Keratan sulphate (KS)
3. Hyaluronan (HA)
4. Heparan Sulphate (HS)

Question 3

True or false: GAGs may be sulphated?

Answer 3

True (except for hyaluronan)

Question 4

Describe the general structure of a proteoglycan (PG)

Answer 4

macromolecules comprised of a core protein with at least one GAG

Question 5

Give 4 functions of proteoglycans

Answer 5

1. conformational activation
2. Enhancing protein-protein interactions (brings proteins together)
3. co-receptor for extracellular ligands
4. cell-surface localisation - tethering of ligands to increase local concentration

Question 6

Give an example of HSPG involved in conformational activation

Answer 6

SARS-CoV-2 spike protein binding to HS induces a conformational change that opens the receptor binding site and facilitates binding to ACE2 and entry into host cell

Question 7

What are the two families of membrane proteoglycans?

Answer 7

Syndecans
Glypicans

Question 8

What is the difference between the two families of membrane proteoglycans?

Answer 8

Syndecans have a membrane spanning core protein

Glypicans have a core protein anchored to the plasma membrane via a Glycosylphosphatidylinositol (GPI) linkage

Question 9

How many members are there of the Syndecan family?

Answer 9

4

Question 10

What is Dally?

Answer 10

A Heparan sulphate Glypican in Drosophila that stands for Division Abnormally Delayed

Question 11

What does Dally do?

Answer 11

Tethers morphogens Dpp and Wg, which have roles in growth. Morphogen signalling occurs when the morhogen reaches a threshold concentration. Mutation in Dally results in delayed division - Drosophila still grow but at a reduce rate

Question 12

True or false: PGs are required for cell signalling?

Answer 12

False: PG stabilises the interaction between the morphogen and the receptor but signalling can still occur in its absence

Question 13

What happens in a Dally mutant?

Answer 13

The morphogen gradient is much shorter - slows down Dpp signalling as concentration threshold takes longer to be reached

Question 14

Which component of the HSPG synthesis are controlled by sugarless, sulfateless and dally genes?

Answer 14

sugarless = UDP-glucose dehydrogenase
sulfateless = N-deacetylase/N-sulfotransferase
dally = PG core protein (glypican)

Question 15

Strucutre and synthesis of HSPG/HS

Question 16

binding sites of particular proteins to HS

Question 17

Role of SULFs (1 and 2) in modification of GAGs.