Fibrous Proteins Flashcards
1
Q
describe the structure of a collagen molecule
A
- triple-helix of 3 protein alpha-chains that are tightly wound
- the alpha-chains are about 1000 amino acids long
2
Q
describe the amino acid composition of collagen
A
- Glycine is found in each 3rd position of the alpha-chain and allows a tight winding of the triple helix
-
proline residues are abundant and lead to “kinks” in the chain
- hydroxyproline residues stabilize the triple helix via H-bonds
-
lysine or modified lysine side-chains form covalent bonds and cross-link tropocollagen
- hydroxylysine residues allow addition of sugars
3
Q
describe the biosynthesis of collagen
A
- synthesized initially as soluble procollagen
- after release into ECM, the propeptides of procollagen are cleaved and the insoluble collagen molecules associate to form a collagen fibril
- extracellular covalent cross-linking with lysine or modified lysine residues form mature collagen fibers
4
Q
describe the biosynthesis of Type I collagen
A
- COL1A1 and COL1A2 lead to
- 2 α-1-chains
- 1 α-2 chain
- α1α2 triple helix
5
Q
describe function of vitamin c in collagen synthesis
A
- Hydroxylation of selected proline and lysine residues done by prolyl hydroxylase and lysyl hydroxylase
- these need vitamin C for reaction
6
Q
describe function of hydroxyproline
A
- hydroxyproline residues allow H-bonds between 3 α-chains
- stabilization of the triple helix
7
Q
describe vitamin c deficiency
A
- scurvy
- decreased stability and tensile strength of collagen leads to:
- bleedings gums
- hemorrhages
- poor wound healing
8
Q
how is winding of the triple helix performed
A
- the N-terminal and C-terminal ends of pro-α chains contain propeptides
- the correct 3 pro-α-chains are first covalently linked at the carboxyl ends by disulfide bonds which allows the formation of a triple helix
- the N-terminal propeptides are also linked to prevent the unwinding
9
Q
name the 3 functions of propeptides
A
- needed in cytosol for the linkage of the correct 3 pro-α chains to each other by disulfide bonds
- allow efficient winding during triple helix formation
- keep the formed procollagen soluble
10
Q
what happens to procollagen after release from cell
A
- propeptides are cleaved by procollagen peptidases
- the formed tropocollagen molecules spontaneously associate to form a collagen fibril
- subsequent cross-linking forms the mature collagen fibers
11
Q
how is extracellular cross-linking performed?
A
- extracellular enzyme lysyl oxidase (copper) deaminates the lysine (or hydroxy lysine) residues
- the enzyme forms free ammonia and an aldehyde residue (allysine)
- allysine forms covalent bonds with other lysine or modified lysine residues
- copper deficiency reduces collagen cross-linking
12
Q
Ehlers-Danlos Syndrome
A
- hereditary connective tissue disorder (>20)
- can result from a mutation of a gene for the pro-α chains of collagen (Type I, III or V collagen)
- Type V collagen defect is the classical form
- Type III collagen defect is the vascular form
- fragility of skin and vascular vessel walls
- most serious and can lead to lethal arterial rupture
13
Q
Osteogenesis imperfecta (OI)
A
- OI Type I is the mildest form
- OI Type II is the most severe form
- OI Type III is severe
- OI Type IV is deforming but with normal sclerae
14
Q
what is the concept of elastin synthesis
A
- Tropoelastin is secreted from fibroblasts into the ECM as a highly soluble linear polypeptide
- The protein fibrillin-1 acts as a scaffold for the extracellular tropoelastin which needs to be cross-linked in order to become the insoluble elastin
- lysyl oxidase forms extracellular allysine residues needed for cross-linking
- formation of desmosine and isodesmosine due to specific cross-linking
15
Q
describe desmosine/isodesmosine
A
- characteristic for elastin and allows it to stretch and bend in any direction
- 3 allysine and 1 lysine residue are covalently linked in desmosine
