Collagen Flashcards
What tri-peptide is found as a regular repeat in fibril-forming collagens?
Gly-X-Y
X=proline
Y=hydroxyproline
Why does hydroxylation of proline stabilize the collagen helix?
Hydroxylation of proline fixes the side chain in the exo conformation, whicih is preferred for proline sidechains in the Y position –> increases collagen’s thermal stability & prevents unwinding
Why does collagen have such high tensile strength?
Multiple interchain hydrogen bonds and dense packing of the triple helix
Mutation of what residue in collagen would be most likely to cause disease and why?
Glycine
Any sidechain other than the hydrogen of Gly would disrupt packing in the collagen triple helix
Post translational modifications of collagen that occur inside the cell
Hydroxylation of Pro & Lys
Glycosylation of hydroxylysine
Disulfide bond formation at C-terminal propeptide extension
Why is vitamin C required for proper collagen fibril formation?
It’s required for prolyl and lysyl hydroxylation, which stabilizes the triple helix
What post-translational modifications of collagen occur after the molecule has been secreted?
Peptidases clip off N- and C-terminal extensions from the procollagen
Lysyl oxidation
Why do some modifications occur inside the cell and some outside?
Prevents the tropocollagen molecule from self-assembling inside the cell
Ehlers-Danlos syndrome
Deficiency in procollagen peptidase
–> carboxyl- and amino-terminal ends of procollagen aren’t cleaved into tropocollagen in the ECM, so fibrils don’t form
–> loose joints
Menke’s syndrome
Defect in copper (Cu) absorption or metabolism–> kinky, steel-colored hair, growth retardation, neural issues
Lysyl oxidase requires Cu2+ as a cofactor to crosslink collagen fibrils
Major collagen type in bones
Type I
Major collagen type in basement membranes
type IV
Why do disorders in type IV collagen cause hereditary nephritis?
Type IV collagen is the major scaffold protein of the basement membrane.
The double basement membrane in the glomerulus is responsible for keeping proteins in the plasma from spilling into the urine during glomerular filtration.
Increased degradation of elastin in the lung causes
emphysema
Fibrillin
Glycoprotein that coats elastin fibers