1.14 ECM 2 Flashcards
4 major proteins found in the ECM
- collagen
- Fibronectin
- Laminin
- elastin
What are 2 adhesion proteins?
fibronectin and laminin - they attach cells to the extracellular matrix
what are the 2 structure proteins?
collagen and elastin - allow stretch and then to return back to original shape
What provides the critical link between cells and their surrounding matrix? - attachment point
Integrins mostly attaches to fibronectin
What is the most abundant fibrous protein and what does it provide?
Collagen - provides tensile strength, regulates cell adhesion, supports chemotaxis and migration and directs tissue development - transcribed and secreted by fibroblasts into sheets and cables
what amino acids are found in collagen?
- glycine - usually first and every third AA
- proline
- hydroxyproline
- hydroxylysine
Is collagen glycosylated?
yes - 3 of the 4 proteins that compose collagen are glycosylated
what are the tandem occurrence orders of collagen composition?
Gly-Pro-X
Gly-Y-Hyp
X and Y are any amino acid
Why is collagen a poor dietary protein?
It is no where close to using all 20 AA to make a complete protein only a couple make up collagen composition
shape of the collagen chain
triple helix -All are constructed from 3 left handed helical peptide chains twisted into a right-handed triple helix - a homotrimer or a heterotrimer - different types of chains yield different types of collagen
Type 1 collagen is found where? - majority of collagen is type 1
skin, bone, tendon, blood vessels, cornea
Type 2 collagen is found where?
cartilage, intervertebral disk, vitreous body
Type 3 collagen is found where?
blood vessels, fetal skin
Type 4 collagen is found where?
basement membrane
what do collagen molecules all aligned in a staggered fashion and cross linked for strength make?
collagen fibrils
Vitamin C is required for?
To hydroxylate proline and lysine
Copper is required for?
hydroxylation of lysine
Steps 1-9 of collagen synthesis
- Synthesis of pro-alpha Chain (ER)
- Hydroxylation of selected prolines and lysines
- Glycosylation of selected lysines
- Self-assembly of 3 pro-alpha chains (Golgi)
- procollagen triple helix formation
- Secretion in secretory vesicle through plasma membrane
- Cleavage of propeptides off of procollagen molecule becomes tropocollagen
- Self-assembly into fibril
- Aggregation of collagen fibrils into collagen fibers
During the cleavage stage of collagen synthesis, what is cleaved off?
the amino and carboxyl terminal groups, this allows the collagen molecules to come together to form the fibril
What holds the collagen fibrils together and what enzyme stabilizes it?
covalent crosslinking lysyl oxidase (LOX) (copper enzyme very reactive makes aldehydes)
What 4 requirements are there for collagen fibrillogenesis?
- fibronectin
- collagen V
- integrin alpha2beta1
- integrin alpha5beta1
What type of collagen is non-fibrillar and why?
type IV - lacks regular glycine (small folds prevent tight helix structure)
- nonhelical hindge in the middle - becomes binding site
- molecule is more flexible
- propeptides not cleaved
- bind head to head or tail to tail to form “network”
3 steps of collagen degradation
- enzymes binding
- unwinding of the triple helix
- cleavage of collagen peptides
What are the 2 enzymes that have the collagenase property to bind and unwind collagen?
- Matrix metalloproteinases (MMPs)
2. Cathepsins (L and K)
What does the initial cleavage yield in collagen degradation?
gelatin - then denaturation and protease digestion followed by phagocytosis
What collagen defect has decreased synthesis of type I with long bone fractures/malformed soft bones?
Osteogenesis imperfecta
What collagen defect is seen in contortionists and causes translucent skin, easy bruising, and arterial/colon rupture?
Ehlers-Danlos
Soluble _________ is secreted into the extracellular space and assembled into elastic fibers (in association with protein FIBRILLIN)
tropoelastin
Elastin synthesis is very similar to what?
collagen sysnthesis
Elastin is rich in amino acids such as glycine alanine valine proline hydroxyproline and lysine but doesnt have any?
hydroxylysine
what 2 conformations are elastin found in?
relaxed and stretched
lysyl oxidase allows elastin to make covalent crosslinks called?
desmosine ring - occurs extracellularly and provides stability
_________ is a point of attachment for cells and is in the form of a dimer
fibronectin
5 things that fibronectin binds
- integrin
- collagen
- fibrin
- heparan sulfate
- proteoglycans
fibronectin has unique __________ which bind it to integrins
binding sites (amino acids)
________is a fibrous and flexible layer that separates organized groups of cells and is secreted by adjacent cells
basal lamina aka tissue divider
4 ECM proteins found in all basal laminae
- laminin
- perlecan (heparan sulfate PG)
- type IV collagen
- entactin/nidogen (glycoprotein)
What is the major protein in the basal lamina and its functions
Laminin (cross appearance)
-trimeric glycoprotein chains covalently linked by disulfide bonds
-short arms =bind to other laminin molecules to make sheets
long arms= binding to cells
what are integrins?
1 cell adhesion receptor that is a dimer (usually heterodimer) works as a ligand binding receptor for fibronectin, collagen, fibrinogen, vitronectin
