Collagen Flashcards
What is the most abundant protein in our bodies?
Collagen
Collagen is made up of how many polypeptides wound around each other to form a rope-like collagen helix?
3
What property of collagen keeps it rigid when most other proteins are clumped up in a hydrophobic mess?
Its triple polypeptide helical domain
Give 3 examples of fiber forming collagens.
Collagens I, II and III
Give an example of a network forming collagen.
Collagen IV
Give a collagen specific sequence of amino acids.
Every third residue is a Glycine i.e. X-Y-GLY-Y-X-GLY…
Collagen is responsible for:
Structural/functional integrity of our body
Collagen self assembles which is followed by stabilization by:
Cross-links - essential for the fiber or network to withstand the physical stresses to which they are exposed.
What three things are necessary for a protein to be called a collagen?
3 protein subunits wound around each other in a helix
Repeating sequence of AAs GLY-AA-AA-GLY-AA-AA…etc
Cross-linking of polypeptides for mechanical strength
Where do the 3 polypeptides form a collagen triple helix?
Intracellularly before being secreted.
What are the two most common AAs found in collagen besides GLY?
Proline and Hydroxyproline
Is the center of a collagen helix hydrophillic or hydrophobic?
Hydrophobic
If you were to look down the center “barrel” of a simple collagen helix, what atom would find down its length?
Hydrogen
One cause of this disease, is a substitution of CYS for GLY in collagen. The strength of collagenous tissues like bone is lowered, leading to multiple fractures.
Osteogenesis Imperfecta
Hydroxyproline and hydroxylysine are AAs of collagen formed in a ______ _______ dependent reaction.
Vitamin C
Proline + alpha-ketoglutarate and O2 and Vit C (via prolyl hydroxylase)»_space;»> ____________
Hydroxyproline
Lysine + Vit C (via lysyl hydroxylase)»_space;»»» __________
Hydroxylysine
Scurvy, a collagen deficiency, is caused by an absence of this in one’s diet:
Vitamin C
This building block of collagen can be measured in urine to estimate collagen turnover:
Hydroxyproline
Hydroxylysine has a special ____ glycosylation in collagen.
O-glycosylation
Collagen is synthesized from 3 proline-___ chains, translated into the ER lumen
alpha chains
List the 4 steps of procollagen synthesis in the ER/Golgi
- Synthesis of PRO-alpha chain.
- Hydroxyation of selected prolines and lysines.
- Glycosylation of selected hydroxylysines
- Self-assembly of three PRO-alpha chains into trimeric helix.
What ensures that PRO-alpha chains are not frame-shifted and are in the right position (“correct register of GLY-X-Y repeats)” before being wound into a helix?
disulfide bonds that form between globular C-terminal ends
On a molecular scale, what causes the symptoms of scurvy?
collagen triple helix does not form because there are not hydroxylated AAs. The hydroxylated AAs raise the melting point of the collagen fibers.
So, not HO-AAs = lower melting point of collagen + normal body temp = degraded/malformed collagen = broken/fragile skin, blisters, ulcers, etc.
What must be removed before fibrillar collagens can become mature collagen ready to self-assemble into fibrils and fibers?
Terminal globular domains - those that helped align the 3 strands to form a triple helix.
Collagen molecules are covalently cross-linked by this enzyme once they are secreted from the cell.
Lysyl oxidase
The covalently bonded cross-link between mature collagen molecules is called a:
Schiff base
The strength of tendons to resist pulling forces is due to:
covalent cross-linking between collagen molecules
If you do not have proper GLY-X-Y repeats, you will have this disease:
Osteogenesis Imperfecta
Failure of proline hydroxylation leads to this disease:
Scurvy
Failure of LYS hydroxylation leads to these two diseases:
Scurvy, Ehlers-Danlos Syndrome (many causes)
Failure of procollagen to process collagen aggregation leads to these diseases:
Ehlers-Danlos & Dermatosparaxis in cattle
Failure of mature collagen to cross-link (no lysyl oxidase) leads to this disease:
Ehlers-Danlos
True or False: Collagen degradation is not very highly regulated.
False, it is highly regulated.
Degradation of collagen requires activation of this enzyme:
Procollagenase (a special matrix metalloproteinase [MMP])
The activity of MMPs is regulated by:
TIMPs
Some bacteria, such as genus Clostridium, use this enzyme to destroy collagenous barriers to infection.
MMPs
What property of Type IV collagen allows it to form a tetramer network?
the globular ends, that were not removed before the collagen was secreted.
Collagen IV is a _______ forming collagen that is a component of basal lamina and other barriers to cells and macromolecules, which self-assemble to form a chain link fence or sievelike structure.
network forming
Type IX collagen is a _____-________ collagen that limits growth of fibers, or enhances the interaction of the fiber with extracellular matrix components.
fibril-associated
Type VII collagen is part of the anchoring fibril that holds _______ onto underlying connective tissue.
epithelium
