L17 Flashcards
Define metizoan
Multicellular animals
Define tissue and give the 4 types and provide examples for each
- several cells of the same origin come together
1. epithelial
2. connective: tendons, ligaments, cartilage
3. muscular: skeletal, cardiac, smooth
4. Neural: neuron, neuroglial
Define Organ
different tissues working together to form a functionally and anatomically distinct part of a body.
What is the ECM
network of proteins and carbs
What 4 molecules make up the ECM?
Proteoglycan
Collagen
Elastin
Multiadhesive proteins
What is the stroma
ECM + associated cells
What is collagen?
is a parallel triple helix (not an Alpha-helix) that has a repetitive sequence with every third residue as glycine. 1050 amino acids long
Where is collagen found?
It is the most abundant protein in mammals (~30% by wt), it is in tendons, cartilage, bones, teeth, skin.
How many isoforms of collagen?
- 16 known isoforms,
- isoforms I, II, and III make up 90% of collagen
What does the core of collagen consist of?
1. repeating Gly-Pro-HyP or 2. Gly-X-Pro/HyP -> X can be any AA, except Trp.
Describe the biosynthesis and secretion of collagen
- Polypeptide synthesis of the Pre-pro-collagen – transported to ER
- PTM: hydroxylation of some P and K
- PTM: some glycosylation
- Form triple helices
Starts at C-term - export across PM
- Termini clipped off, processed pro-collagen
- Tropocollagen associate into fibrils
- cross-links between Lys and Hyl residues
Draw the chemical rxn for hydroxyproline formation
Slide 6
How is hydroxyproline essential for collagen stability?
- Inc MT: A peptide w/10 Gly–Pro–Pro repeats will fold to form a collagen triple helix, but the structure melts at 41 °C vs. if the 10 repeats are changed to Gly–Pro–4-Hyp, the melting temperature jumps to 69 °C.
- Water molecules help to bridge H-bonds between chains
How does hydroxyproline essential for collagen stability?
- Tight packing of Gly, forms hydrophobic core in Collagen
2. Inserting Ala (orange sticks) into Gly position leads to a loss in collagen stability.
Draw cross-linking of collagen
- Peptidyl-lys
- – lysyl oxidase (deanimates peptidyl-Lys to the corresponding aldehyde) –> - Peptidyl-allysine
- Lysine-norleucin cross link (an aldimine)
- Pyridinodine
Fxn of matrix metalloprotease (MMP)?
Remodelling of collagen/ECM by cleavage
- degrades diff proteins in the ECM
Examples of matrix metalloproteases
Collagenases, gelatinases
How many different matrix metalloproteases are there? How are they activated?
- 28 diff MMP
2. MMPs secreted as zymogens and activate each other by cleavage of a propeptide
What is the structure of MMPs? Conserved sequence?
- B-helix stabilized by Ca2+
- Catalytic Zn2+ and water in active site
- Conserved sequence: His-Glu-X-X-His-X-X-Gly-X-X-His
Draw the typical metallo-protease mechanism
Slide 13
How are MMPs regulated?
4 tissue inhibitors of matrix metalloproteases: TIMP1, TIMP2, TIMP3, TIMP4
Describe the structure of elastin
- 750 AA’s in length
- Forms elastin fibres
- Nonglycosylated, contains no Hyl, and very little Hyp
Draw the mechanism for cross-linking of elastin desmosine
Slide 16
