lecture 10 Flashcards
what are the fibril forming collagens?
1,2,3,5,11,24,27
what are the beaded filaments?
6
what’re the anchoring fibrils?
7
what are the network collagens?
4,8,10
what are the collagens anchoring basement membranes to stroma?
15,18
what are the collagens with trans-membrane domains?
13,17,25
what causes the stability of collagen?
- covalent cross links
what forms the stability?
- 2 lysine resides joined to form aldol crosslink
- by enzyme Lysyl oxidase
what are the syndromes associated with collagen ?
- ehlers-danlos syndrome type 5
- spontaneous coronary artery dissection
what occurs in ehlers-danlos syndrome type 5?
- collagen cross links aren’t formed properly
- causes flexibility and stretchiness in wrong places
- stretchy skin
what occurs in spontaneous coronary artery dissection?
- splits due to collagen being ineffective at holding vessel together (heart attack)
what do mutations in COL9 and 11 cause?
-chondrodysplasia syndromes (short in stature, abnormal development of bones)
what type of collagen increases in osteoarthritis?
- type 3
what are proteoglycans?
- 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
what is the bottle brush structure?
- central protein core
- glycosaminoglycans attached (GAGs)
what is the charge of glycosaminoglycans?
- highly negative
- due to lots of ester sulphate and carboxylic acid groups
what is aggrecan?
- proteoglycan found in cartilage
- aggregates
what is the structure of aggrecan?
- 3 globular domains on protein core (G1,2,3)
- keratan chains
- chondroitin chains
what is the G1 domain used for?
- important in aggregation
what is the structure of keratan chains ?
- negative charged
- shorter
- galactose
what is the structure of Cs chains?
- regularly spaced in Cs1
- clusters in Cs2
- glucuronic acid
what is the specific linkage found in GAGs?
- involves serine or threonine to link Ks to Cs
- glucuronic acid, galactose, galactose- xylose = Cs repeat
what is present in a single aggrecan molecule?
- 100 Cs chains
- 30-60 Ks. chains
- overall high negative charge
what is the composition of the aggrecan protein core?
- G1 = N terminal globular region that interacts with another glycosaminoglycan
- hyaluronan (not sulphated, free and not bound)
what is the purpose of hyaluronan?
- dampens compressive forces on joint in synovial fluid
what occurs as result of interaction with hyaluronan?
- proteoglycan linking vis ionic interaction
- stabilised by link protein
- size deponent on size of hyaluronic acid
what is the purpose of this?
- trap in collagen net
what are proteoglycans present in extracellular matrix as?
- multimolecular aggregates
what do the aggregates consist of?
- many proteoglycan monomers bound to single molecule of hyaluronan by ionic interaction
what is the importance of hyaluronan?
- both functional copies of HAS2 = normal size limb
- HAS2 removed = improper joint formation, shorter limbs
what are the similar domains present in link protein, G1 and G2?
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
what is the function of G2?
- unknown
where interacts with hyaluronon?
- N terminal
- B domain
what is purpose of A domain?
- link Protein binding to A domain
what are the key interactions in G1 allowing aggregation to take place?
- 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
what groups are necessary for the interaction with G1?
- 4 carboxyl groups
- 3 or more N-acetyl groups
how is the minimum chin length of hyaluronan determines for aggregation?
- 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
how does gel filtration work?
- beads in column
- substance added to top
- small fit through the gaps towards bottom
- if big, it moves quicker down the outside
