ECM Flashcards
What are the 3 major AA types in collagen?
- Glycine (1/3)
- Proline (1/4)
- Lysine
*Pro and Lys are very often hydroxylated
What is a very common AA sequence?
Gly-X-Y
X is usually Pro
Y is usually hydroxyPro
What is the secondary/tertiary structure of collagen?
Type II trans helix (2.8 angstrom rise per AA along the fiber axis).
What is the quaternary structure of collagen? What is it called?
R handed triple helix
Each chain (of the 3) is an Alpha chain, called Tropocollagen as a whole
What causes osteogenesis imperfecta?
Replacement of glycine with a bulkier AA prevents tight binding of triple helix.
Why are alpha chain-encoding genes so much longer than the final polypeptide?
N-terminal extension and C-terminal extension
Where does hydroxylation of proline and lysine occur?
ER
How is proline hydroxylated and what is an important co-factor?
Prolyl hydroxylase hydroxylates C$ using ascorbate as a co-factor.
What disease occurs when ascorbate is missing from the diet?
Scurvy: skin lesions, fragile blood vessels, poor wound healing.
Why is hydroxylation important?
It is required for cross-linking of collagen molecules.
How is lysine hydroxylated? Does it require a cofactor?
Lysyl hydroxylase. Yes, also requires ascorbate
Which common collagen AA can also be glycosylated?
(Hydroxy)Lysine
How does hydroxyproline affect Tm?
Increases it
How is pro-collagen converted into tropocollagen and where?
N and C terminal peptidases in the extracellular space.
What creates the striated appearance of collagen?
asymmetric 1/4 stagger
How are collagen fibers stabilized?
- Covalent crosslinking of lysine into an aldehyde by lysyl oxidase (LOX)
- Formation of hydroxypyridnium ring (pyridinoline) between 2 hydroxyllysyl and 1 lysyl residues
What causes the disease lathyrism?
Ingestion of BAPN from sweet peas which inhibits LOX, thus destabilizing collagen fibers
How does the body degrade collagen for regular turnover and repair?
Matrix metalloproteinases (MMPs) cleave the collagen triple helix 75& from the N terminus, lowering the Tm and allowing for denaturation at body temp.
Which AAs make up elastin?
- Proline
- Glycine
- Valine
Describe elastin’s structure/properties.
No regular secondary structure
Hydrophobic/highly insoluble
Describe the “maturation” of elastin fibers.
70kDa monomer called tropoelastin -> secreted to extracellular space -> crosslinking by LOX forming a “desmosine” link (now insoluble fiber)
What enzyme mediated elastin turnover and how quick is it?
Elastase - On the order of years
What causes emphysema?
Destruction of the elastin fibers in the alveolar epithelia of the lungs. Destruction of walls results in large air gaps and reduced SA for exchange.
What enzyme if defective is involved in Menkes kinky-hair syndrome and Ehlers Danlos, among others?
LOX (lysyl oxidase)
