lecture 10 Flashcards

1
Q

what are the fibril forming collagens?

A

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

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2
Q

what are the beaded filaments?

A

6

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3
Q

what’re the anchoring fibrils?

A

7

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4
Q

what are the network collagens?

A

4,8,10

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5
Q

what are the collagens anchoring basement membranes to stroma?

A

15,18

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6
Q

what are the collagens with trans-membrane domains?

A

13,17,25

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7
Q

what causes the stability of collagen?

A
  • covalent cross links
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8
Q

what forms the stability?

A
  • 2 lysine resides joined to form aldol crosslink
  • by enzyme Lysyl oxidase
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9
Q

what are the syndromes associated with collagen ?

A
  • ehlers-danlos syndrome type 5
  • spontaneous coronary artery dissection
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10
Q

what occurs in ehlers-danlos syndrome type 5?

A
  • collagen cross links aren’t formed properly
  • causes flexibility and stretchiness in wrong places
  • stretchy skin
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11
Q

what occurs in spontaneous coronary artery dissection?

A
  • splits due to collagen being ineffective at holding vessel together (heart attack)
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12
Q

what do mutations in COL9 and 11 cause?

A

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

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13
Q

what type of collagen increases in osteoarthritis?

A
  • type 3
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14
Q

what are proteoglycans?

A
  • 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
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15
Q

what is the bottle brush structure?

A
  • central protein core
  • glycosaminoglycans attached (GAGs)
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16
Q

what is the charge of glycosaminoglycans?

A
  • highly negative
  • due to lots of ester sulphate and carboxylic acid groups
17
Q

what is aggrecan?

A
  • proteoglycan found in cartilage
  • aggregates
18
Q

what is the structure of aggrecan?

A
  • 3 globular domains on protein core (G1,2,3)
  • keratan chains
  • chondroitin chains
19
Q

what is the G1 domain used for?

A
  • important in aggregation
20
Q

what is the structure of keratan chains ?

A
  • negative charged
  • shorter
  • galactose
21
Q

what is the structure of Cs chains?

A
  • regularly spaced in Cs1
  • clusters in Cs2
  • glucuronic acid
22
Q

what is the specific linkage found in GAGs?

A
  • involves serine or threonine to link Ks to Cs
  • glucuronic acid, galactose, galactose- xylose = Cs repeat
23
Q

what is present in a single aggrecan molecule?

A
  • 100 Cs chains
  • 30-60 Ks. chains
  • overall high negative charge
24
Q

what is the composition of the aggrecan protein core?

A
  • G1 = N terminal globular region that interacts with another glycosaminoglycan
  • hyaluronan (not sulphated, free and not bound)
25
Q

what is the purpose of hyaluronan?

A
  • dampens compressive forces on joint in synovial fluid
26
Q

what occurs as result of interaction with hyaluronan?

A
  • proteoglycan linking vis ionic interaction
  • stabilised by link protein
  • size deponent on size of hyaluronic acid
27
Q

what is the purpose of this?

A
  • trap in collagen net
28
Q

what are proteoglycans present in extracellular matrix as?

A
  • multimolecular aggregates
29
Q

what do the aggregates consist of?

A
  • many proteoglycan monomers bound to single molecule of hyaluronan by ionic interaction
30
Q

what is the importance of hyaluronan?

A
  • both functional copies of HAS2 = normal size limb
  • HAS2 removed = improper joint formation, shorter limbs
31
Q

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

A

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

32
Q

what is the function of G2?

A
  • unknown
33
Q

where interacts with hyaluronon?

A
  • N terminal
  • B domain
34
Q

what is purpose of A domain?

A
  • link Protein binding to A domain
35
Q

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

A
  • 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
36
Q

what groups are necessary for the interaction with G1?

A
  • 4 carboxyl groups
  • 3 or more N-acetyl groups
37
Q

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

A
  • 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
38
Q

how does gel filtration work?

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