ECM Flashcards
collagen
main structural protein in extracellular space in connective tissue
the most abundant protein in animal kingdom
triple helix
all have same basic structure, but w/ variations
3 types of collage need to know:
Type I. Fibril-forming
Type IV. Network-forming
Type VII. Attachments of basal animae to underlying connective tissue
Type I Collagen
found places where you need strong forces
not flexible
fibrils are stacked layers, alternating parallel and antiparallel segments
N and C terminals cleaved
bone, cartilage, and cornea
Type IV Collagen
network attached to each other at N and C terminals forming dimers and trimers
found in filtering apparatus of kidney
flexible due to breaks in the collagen triple helix
Type VII Collagen
anchoring connect collagens have C and N terminals no breaks more flexible than I, but not as flexible as IV, does not bend
Diseases affecting 3 dif types of collagen
Type I -> Osteogenesis imperfecta
Type IV -> Alport Syndrome
Type VII -> dystrophic Epidermolysis bullosa
osteogenesis imperfecta
affects type I collagen by a change in the gene sequence: gly (very small) is replaced w/ ser (much bigger) –> protein doesn’t fold/pack correctly and can’t be secreted from the cell to form collagen I
w/o collagen I bones don’t properly form
bones weak and fracture easily
Alport Syndrome
affects type IV collagen
leads to kidney failure -> can’t filter blood
hair loss and eye problems occur
Dystrophic epidermolysis bullosa
affects type VII collagen
anchoring fibrils in the dermis break
patients have breaks in the dermis, causing the skin layers to separate
blisters appear, skin comes off
Junctional Epidermolysis Bullosa
defect in laminin 5
causes epidermis to separate from the dermis at the basement membrane
Simplex Epidermolysis Bullosa
defect in intermediate filament
effects keratin in the epidermis
mildest and most common form of epidermolysis bullosa
proteoglycans
carbohydrates with attached proteins that are important ECM structural molecules
are often necessary for certain growth factors to work:
first, GF binds to proteoglycan, then heparanase clips the heparan sulfate, that is attached to the GF, from the proteoglycan; once GF and attached HS are free, the GF can bind to its receptor
angiogenesis utilizes this: GF and attached HS bind to receptors on the blood vessel promoting growth
fibrillin
extracellular structural protein that is important in creating elasticity
found in the eyes and aorta
Marfan Sydrome
defect, or lack of , fibrillin
lack the elasticity needed in certain areas of the body, particularly the aorta
people with this have elongated limbs because GF TgF-beta that normally binds fibrillin, accumulates and stimulates growth of limbs
fibronectin
ECM molecule with multiple purposes. Different kinds of fibronectin all come from singular gene, but alternate splicing yields mult kinds
it has different regions, or domains, of specific binding
ECM adhesive protein
important in blood clotting, wound healing, and cell binding
fibronectin interacts w/ an integrin in cell binding
Staph bacteria use fibronectin to bind to cells
fetus uses to attach to uterus; if high levels of fibronectin are detected after 22 weeks, the fetus will probably be premature because it is not attached well
laminin
adhesive extracellular protein w/ 3 chains: alpha, beta, gamma
each chain has different isoforms
can form many combinations for specific binding
laminin5 (affected in junctional epidermolysis bullosa) is in the basement membrane of the skin tissue, it binds the epidermis to the dermis
