Lecture 15: Collagen, Elastin, ECM

Question 1

Collagen

Answer 1

Most abundant protein in the body (~30% of all proteins)

Primary building block for skin, muscles, bones, etc., I-V are five main types

Question 2

Collagen composition

Answer 2

Made of helical alpha chains ~1000 AAs long; 33% Gly, 17% Pro.
Gly-X-Y pattern (X often = Pro, Y often = Pro-OH); alternating non-polar/polar pattern Gly-Pro-Y // Gly-X-Y etc.

Question 3

Hydroxylation of collagen

Answer 3

Post-translational modification; hydroxylation of Pro, Lys by prolyl/lysyl hydroxylase using Vitamin C (ascorbate) as a cofactor

Question 4

Glycosylation of collagen

Answer 4

Post-translational modification; addition of GAL (and sometimes GLC on top) to Lys-OH by galactosyl/glucosyl transferase

Question 5

Collagen structure

Answer 5

1. 3 alpha chains -> procollagen triple helix (Type 1 = 2x α1 chains + 1x α2 chains) extruded from cell
2. Procollagen peptidase cleaves non-helical N/C termini -> tropocollagen
3. Tropocollagen 1/4 stagger -> collagen fiber
4. Collagen fiber crosslink by LOX

Question 6

Collagen crosslinking

Answer 6

Covalent X-linking btwn collagen fibers stabilizes structure. Lysyl oxidase -> reactive aldehydes on Lys/Lys-OH; requires copper.

Question 7

Osteogenesis imperfecta

Answer 7

Group of diseases characterized by bone fragility due to α1/α2 Type 1 collagen chain mutants; varying severity

Question 8

Scurvy

Answer 8

Lack of vitamin C -> no preprocollagen hydroxylation

Question 9

Ehlers-Danlos Syndrome

Answer 9

Lysyl hydroxylase deficiency; autosomal recessive; stretchy skin, hypermobility, ocular fragility

Question 10

Elastin

Answer 10

Gives tissues elasticity; single, non-glycosylated molecule. Very slow turnover (years), broken down by elastase

Question 11

Elastin composition

Answer 11

~33% Gly, ~50% Pro (notice higher proline content vs collagen)

Question 12

Elastin structure

Answer 12

Synthesized and secreted as tropoelastin (70 kDa soluble monomer) -> cross-linked by lysyl oxidase into highly insoluble fibers

Question 13

α1 antitrypsin protein deficiency

Answer 13

AAT is a Ser protease inhibitory that inhibits human neutrophil elastase; AAT deficiency leads to emphysema due to alveolar damage and liver damage in children (retention + polymerization of mutant AAT in liver ER)

Question 14

Matrix metalloproteases

Answer 14

Enzymes that degrade ECM components; e.g. path clearing for vasculature, degrading intercellular junctions

Question 15

Proteoglycans + GAGs

Answer 15

Form hydrated ground substance in CT. Facilitate cell-protein interactions, can protect proteins from degradation, serves as a growth factor reservoir

Question 16

Fibronectin

Answer 16

High MW glycoprotein (dimer linked by 2 disulfide bonds). Binds ECM components, signaling molecules, polysaccharides, and cell surface receptors (e.g. integrin signalling)

Question 17

ECM and cancer

Answer 17

The ECM has a huge role in cancer pathogenesis due to its jobs in forming barriers, migration tracks, storing growth factors, and mediating cell signaling