lecture 10

Question 1

what are the fibril forming collagens?

Answer 1

1,2,3,5,11,24,27

Question 2

what are the beaded filaments?

Answer 2

6

Question 3

what’re the anchoring fibrils?

Answer 3

7

Question 4

what are the network collagens?

Answer 4

4,8,10

Question 5

what are the collagens anchoring basement membranes to stroma?

Answer 5

15,18

Question 6

what are the collagens with trans-membrane domains?

Answer 6

13,17,25

Question 7

what causes the stability of collagen?

Answer 7

• covalent cross links

Question 8

what forms the stability?

Answer 8

• 2 lysine resides joined to form aldol crosslink
• by enzyme Lysyl oxidase

Question 9

what are the syndromes associated with collagen ?

Answer 9

• ehlers-danlos syndrome type 5
• spontaneous coronary artery dissection

Question 10

what occurs in ehlers-danlos syndrome type 5?

Answer 10

• collagen cross links aren’t formed properly
• causes flexibility and stretchiness in wrong places
• stretchy skin

Question 11

what occurs in spontaneous coronary artery dissection?

Answer 11

• splits due to collagen being ineffective at holding vessel together (heart attack)

Question 12

what do mutations in COL9 and 11 cause?

Answer 12

-chondrodysplasia syndromes (short in stature, abnormal development of bones)

Question 13

what type of collagen increases in osteoarthritis?

Answer 13

• type 3

Question 14

what are proteoglycans?

Answer 14

• protein and Vulcan (polysaccharide)
• special class of glycoproteins
• usually low protein, high CHO
• polysaccharide chains are glycosaminoglycans
• joined by reducing terminal sugar residues
• bottle brush confirmation

Question 15

what is the bottle brush structure?

Answer 15

• central protein core
• glycosaminoglycans attached (GAGs)

Question 16

what is the charge of glycosaminoglycans?

Answer 16

• highly negative
• due to lots of ester sulphate and carboxylic acid groups

Question 17

what is aggrecan?

Answer 17

• proteoglycan found in cartilage
• aggregates

Question 18

what is the structure of aggrecan?

Answer 18

• 3 globular domains on protein core (G1,2,3)
• keratan chains
• chondroitin chains

Question 19

what is the G1 domain used for?

Answer 19

• important in aggregation

Question 20

what is the structure of keratan chains ?

Answer 20

• negative charged
• shorter
• galactose

Question 21

what is the structure of Cs chains?

Answer 21

• regularly spaced in Cs1
• clusters in Cs2
• glucuronic acid

Question 22

what is the specific linkage found in GAGs?

Answer 22

• involves serine or threonine to link Ks to Cs
• glucuronic acid, galactose, galactose- xylose = Cs repeat

Question 23

what is present in a single aggrecan molecule?

Answer 23

• 100 Cs chains
• 30-60 Ks. chains
• overall high negative charge

Question 24

what is the composition of the aggrecan protein core?

Answer 24

• G1 = N terminal globular region that interacts with another glycosaminoglycan
• hyaluronan (not sulphated, free and not bound)

Question 25

what is the purpose of hyaluronan?

Answer 25

- dampens compressive forces on joint in synovial fluid

Question 26

what occurs as result of interaction with hyaluronan?

Answer 26

- proteoglycan linking vis ionic interaction - stabilised by link protein - size deponent on size of hyaluronic acid

Question 27

what is the purpose of this?

Answer 27

- trap in collagen net

Question 28

what are proteoglycans present in extracellular matrix as?

Answer 28

- multimolecular aggregates

Question 29

what do the aggregates consist of?

Answer 29

- many proteoglycan monomers bound to single molecule of hyaluronan by ionic interaction

Question 30

what is the importance of hyaluronan?

Answer 30

- both functional copies of HAS2 = normal size limb - HAS2 removed = improper joint formation, shorter limbs

Question 31

what are the similar domains present in link protein, G1 and G2?

Answer 31

link = globular domain, immunoglobulin like fold, proteoglycan tandem repeats G1 = immunoglobulin like fold, proteoglycan tandem repeat, a and 2 Bs G1 = 2 b domians, no A domain

Question 32

what is the function of G2?

Answer 32

- unknown

Question 33

where interacts with hyaluronon?

Answer 33

- N terminal - B domain

Question 34

what is purpose of A domain?

Answer 34

- link Protein binding to A domain

Question 35

what are the key interactions in G1 allowing aggregation to take place?

Answer 35

- intact disulphide bridges 5-7 to maintain the globular structure of G1 region - intact arginine and tryptophan residues to maintain globular G1 confirmation - free e-amino groups on line to keep the correct ionic charge of the domain

Question 36

what groups are necessary for the interaction with G1?

Answer 36

- 4 carboxyl groups - 3 or more N-acetyl groups

Question 37

how is the minimum chin length of hyaluronan determines for aggregation?

Answer 37

- add long chain hylauronic acid so aggregate forms - viscosity increases due to size differences - add short chain hyaluronic acid in excess - proteoglycans have choice of what to bind to - if short binds causes drop in viscosity

Question 38

how does gel filtration work?

Answer 38

- beads in column - substance added to top - small fit through the gaps towards bottom - if big, it moves quicker down the outside