ECM and Collagen

structural proteins in the extracellular matrix include [ ] - the most abundant - and [ ]

collagen

elastin

adhesive glycoproteins in the extracellular matrix include [ ], [ ], and [ ]

fibronectin, laminin, and chondronectin

proteoglycans and GAGs are core proteins [ ] attached to glycosaminoglycans

covalently

structural support, elasticity, [ ], and migration are functions of the extracellular matrix

cell signaling

in the [ ] structure of collagen, each alpha chain forms a left-handed helix

secondary

in the tertiary structure of collagen, three alpha helices twist into [ ]

a right-handed triple helix (tropocollagen)

in the quaternary structure of collagen, [ ]

tropoollagen molecules assemble into fibrils and fibers

the amino acids found in collagen include [ ], [ ], [ ], and [ ]

glycine, proline, hydroxyproline, and hydroxylysine

glycine on every [ ] [ , allows for [ ] [ ]

third residue

tight packing

proline and hydroxyproline stabilize the helix via [ ] [ ]

Hydrogen bonding

hydroxylysine are sites for [ ], cross-links

glycosylation

what are the steps in collagen biosynthesis

translation of pre-collagen

hydroxylation of proline/lysine

glycosylation

triple-helix formation » procollagen

secretion to extracellular space

propeptide cleavage by extracellular peptidases » tropocollagen

self-assembly into fibrils

cross-linking via lysyl oxidase forming mature fibers

the post-translational modification [ ] of proline and lysine requires [ ], [ ], and [ ]

hydroxylation

O2, Fe2+, Vitamin C [ascorbate]

[ ] has no Gly-X-Y repeats of hydroxylysine

elastin

elastin lacks [ ] [ ] and [ ]

triple helix and sugars

elastin contains unique cross-links [ ] and [ ] giving it its elasticity

desmosine & isodesmosine

[ ] is rich in glycine, proline, hydroxyproline, and hydroxylysine

collagen

collagen forms cross-links via [ ] and [ ]

lysine and hydroxylysine

copper is the cofactor for [ ] [ ] that cross-links collagen and elastin

lysyl oxidase

[ ] is required for hydroxylases, it activates oxygen

Iron

[ ] [ ] is a reducing agent for hydroxylases, a deficiency leads to scurvy

ascorbic acid

Vitamin C

α₁-Antitrypsin (α₁-AT) is an inhibitor that

inhibits elastase (key in lungs) and collagenase

α₂-Macroglobulin is an inhibitor that

neutralizes elastase, collagenase, and trypsin

an imbalance in [ ] leads to emphysema

α₁-AT deficiency

mutations in COL1A1/1A2 replaces glycogen allowing for improper folding leads to [ ] [ ]

Osteogenesis Imperfecta

mutations or enzyme deficiencies lead to hyperelastic skin, and hypermobile joints

Ehlers-Danlos Syndrome

a vitamin C deficiency [ ] leads to impaired triple helix formation

Scurvy

[ ] [ ] is a mutation in fibrilin-1

Marfan Syndrome

Marfan Syndrome creates [ ] [ ] [ ] leading to skeletal, ocular, and cardiovascular defects

weak elastic fibers

[ ] are repeating disaccharides of uronic acid or galactose + hexosamine and are often sulfated

GAGs

types of GAGs include

hyaluronic acid

chondroitin 4/6-sulfate

keratan sulfate I/II

heparin

heparan sulfate

dermatan sulfate

explain how GAGs are attached to proteins

they’re linked to serine or threonine residues of a core protein

UDP-sugars add units [ ] and the [ ] provides sulfate

sequentially, PAPS

a deficiency of lysosomal hydrolases leads to

lysosomal accumulation of GAGs (Hurler’s Syndrome )

the roles of adhesive glycoproteins include

wound healing

cell adhesion

migration

spreading

chemotaxis

matrix metalloproteinases work to ?

degrade ECM protiens

enable tissue growth, differientiation, migration

matrix metalloproteinases are inhibited by ?

TIMPs - tissue inhibitors of metalloproteinases preventing excessive ECM breakdown