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what protein makes up 10-20% of protein mass
collagen
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characteristics of collagen
- very stable
- contains glycine, proline, and hydroxyproline
- 42 exons, repeats of GXY
- left handed helix, glycines on one side
- 3 single helixes form right helix with prolines on outside
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translation of collagen
- insert preprocollagen in ER during translation
- N-terminal sequence is cleaved -->procollagen
- procollagen entirely unfolded
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post-translational modifications to Collagen
- proline hydroxylases on Y prolines, uses cofactor ascorbic acid
- glycosylation on lysines- adds gal or glu-gal
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Structure of 3 unfolded propeptides
- a c-terminal globular peptide connected to an alpha chain
- the three zip up from C to N-terminus
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benefit of C to n zip up of collagen
- prevents non-specific disorder assembly
- sets register
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what happens as zipper binds the three alpha helices together
polypeptide isomerase converts all prolines to trans
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rate limiting step of collagen zip up
polypeptide isomerase
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how is procollagen transported out of Golgi
special variance of COPII vesicles transfer it outside of membrane
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what is the final step to make a mature collagen trimer
matrix metallo protease cleaves C-terminal propeptide, uses Zn ion
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function of lysyl oxidase
crosslinks various lysines between 2 trimers to strengthen whole tissue
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Elastic Fibers
rubbery, made from 3 components(Elastin, Fibrillin, something else)
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Elastin characteristics
90% of filter biomass, alpha helix connected to alpha helix, flexible, long and relatively unstructured
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Fibrillin
multiple globular domains in a pattern with flexibility, long, and relatively unstructured
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Fibrillin and disease
faulty fibrillin results in Marfan Syndrome
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GAGs
Glycosaminoglycans - long polysaccharide comprised of dozens to hundreds repeats of a disaccharide
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where are GAGs produced
in the golgi
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proteoglycans
proteins with GAGs on it
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Structure of GAGs and Proteoglycans
large, hydrophillic, charged and bind large quantities of water, mechanically labile structure, not strong
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ex. of PG
in synovial fluid used to lubricate joints, mucus molecules in membranes
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ex. of GAG
collagen GAGS is vitreous humor of the eye
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Adhesive glycoproteins ex.
fibronectin-multiple families large molecules ~235 Da, forms haro dimer
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what does fibronectin bind to
collagens, fibrins, and other PG
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what does fibronectin contain
specific RGD sequence - (arg, gly, asp) bind to integrins
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what are integrins
cell surface receptors that bind to RGD sequence of fibronectin
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What is the Basal Lamina
thin sheet that surrounds muscle and peripheral nerve tissue and lies underneath and provides filtration under kidney
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components of basal lamina
laminin and collagen IV
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structure of laminin
a heterotrimer w/ unique forms a 2-D sheets secreted by epithelium itself and muscle cells
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How do cancer cells metastasize
- cells have upregulation mutations that increase matrix metalloproteases
- that digest EC and move and rebuild it as they move
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what determines if cells migrate/crawl
density of matrix, not too low or high, just right in the middle
and CAMS
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common case for breast cancer and EC matrix
collagen density is often ideal for metastasis
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Cell Adhesion Molecules (CAMs)
- 6 families of molecules
- invidual weak interactions- high avidity
- involved in information processing, send signals to the cytoskeleton, and signal transduction
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3 types of CAMs
IgCam, Cadherin, Integrins
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