Biochemistry of Collagen Flashcards
What is ECM?
ECM is the acellular componenant of tissue
What percentage of an adult is cells and what percent is ECM?
80% cells, 20% ECM
What does ECM do?
- Provides a scaffold for tissue development
- Transmits force (particularly compression) - look at cartilage and intervertebral discs
- Provides a mechanical basis for cell attachment and movement (sort of like providing the attachment site for a pole vault stick)
- Provides survival signals for STEM cells to keep them as STEM cells
What are the two types of ECM and what are they?
- The Interstitial Matrix. The interstitial matrix is the connective tissue
- The Basement Membrane.
What is ECM made of?
- 50% water
- Proteins
- Glycoproteins (proteins with sugars attached)
- Proteoglycans (have a GAG side chain which binds and traps water providing protection against compression - like a water mattress). Glycosaminoglycans = GAGs.
What is collagen? Where is it found?
Collagen is a major component of connective tissue.
What is the gross structure of collagen fibres? Why?
Striated, no crossing over - this allows lengthening and shortening.
How is collagen formed? What about its composition allows it to form its structure?
Collagen is formed in the Endoplasmic Reticulum. Collagen requires its 3 alpha chains to come together and form a triple helix.
- It can do this because its amino acid structure is the repeating pattern of ‘Gly-X-Y’. This means every 3rd amino acid is a glycine (the smallest amino acid, remember Glycine’s R group is just a hydrogen), meaning the collagen helix can have miniscule space between it, only enough for the smallest amino acid and so will be very tightly packed. X and Y means it can be any amino acid, but it is often Proline and Hydroxyproline
How can mutations in collagen cause defects?
As collagens are present in many tissues and organs, mutations in collagens can impact many different areas - making treatment very difficult as numerous areas have to be dealt with.
How is collagen matured?
As the 3 alpha chains are forming the triple helix in the ER they are being modified. They are being Hydroxylated - the addition of a hydroxyl group to the prolines and lysines which are present - this allows the proteins to be folded correctly. Additionally, hyroxylated lysines are modified further by addition of sugar molecules. Once the triple helix is formed, these modifications stop. These alpha chains come together into a collagen protein which is further modified as pro-peptides (which are not part of the triple helix) are cleaved off - leaving perfect triple helical structures (fibrils) which arrange themselves into larger fibres.
Why are damages to collagen not repaired?
As collagen is a very stable protein and has a half-life of 100 years, meaning collagen laid down early in life is what you are stuck with - there is no repair mechanism.
What amino acid do collagen mutations most commonly impact?
Glycine as it is integral for collagen function.
What is Ostegenesis Imperfecta or ‘Brittle Bones Disease’ caused by?
The disease can be inherited and is due to mutations in COL1A1 and COL1A2 which together form Collagen I trimers. Mutations causing OI can be stop codons, promoter mutations or mRNA instability.
Describe differences between different severities of OI?
- Mild OI = Low levels of collagen I
- More severe forms - Composition of collagen is changed, mostly due to glycine mutations which mean the protein is trying to fold but cannot. This causes further modification of these polypeptides as the ‘perfect triple helix’ cannot be formed and so the sugar molecules are continually added = making bigger, heavier non-functioning proteins.
