II. Post-transcription | 28. Types, structure and synthesis of collagen Flashcards
I. Types of collagen
1. What is collagen?
- Collagen is a fibrous protein secreted by CT cells and makes up 25% of all of the protein in our body
- It is stretch-resistant
I. Types of collagen
2. What are the 4 main types of collagen?
I. Types of collagen
3. What are the structure of occurrent of type I Collagen?
- Structure: wide fibre
- Occurence: tendons, bones
I. Types of collagen
4. What are the structure of occurrent of type II Collagen?
- Structure: narrow fibre, crosslinks
- Occurence: cartilage, vitreous body
I. Types of collagen
5. What are the structure of occurrent of type III Collagen?
- Structure: more elastic
- Occurence: blood vessels, skin
I. Types of collagen
6. What are the structure of occurrent of type IV Collagen?
- Structure: extensive crosslinks
- Occurence: basement membrane
II. Structure of collagen - Primary structure of collagen
1. Describe the primary structure of collagen
- The characteristic primary structure is (Gly-Pro-Hyp)n (Hyp = 4-hydroxyproline)
- Each 3rd AA in the sequence must be glycine. The other substituents are: alanine, proline and hydroxyproline
- Collagen is very rich in glycine and proline
II. Structure of collagen - Primary structure of collagen
2. What is the effect of glycine in primary structure of collagen?
- Glycine has the smallest side group of all the AAs (only one H+) which makes proteins very elastic if they have too much of it.
- Glycine constitute about 1/3 of collagen
- Since too much glycine in a protein makes it very flexible, it is typically not a large part of proteins, except for in collagen
II. Structure of collagen - Primary structure of collagen
3. What is the effect of Proline in primary structure of collagen?
Proline is a special AA, in that an alpha-amino group is part of the ring structure this AA forms
-> makes proline very rigid, therefore proline is not found abundantly in proteins
=> Combination of glycine (very flexible) and proline (very rigid) = good balance
II. Structure of collagen - Secondary structure of collagen
4. Describe the secondary structure of collagen
- Refers to the formation of a polyproline helix, which resembles an alpha-helix -> is looser than alpha-helix = 1 turn of the polyproline helix is larger than that of an alpha-helix
II. Structure of collagen - Secondary structure of collagen
5. What is the reason for the loose structure of the polyproline helix?
The reason for the loose structure of the polyproline helix is the proline repulsion H-bond donor/acceptor atoms that become too far from each other
=> this large distance between the hydrogen bond donor and acceptor atoms makes the polyproline helix instable
II. Structure of collagen - Secondary structure of collagen
6. What is the solution for the polyproline helix?
The solution is that 3 polyproline helices are put together /polymerized, and forms a more stable structure due to inter-chain hydrogen bond
=> forming a collagen superhelix consisting of 3 polyproline helices
II. Structure of collagen - Secondary structure of collagen
7. How are the inter-chain H-bonds formed in Secondary structure of collagen?
The inter-chain H-bonds are formed between -NH (amino) and -CO (carboxyl) groups of the peptide bonds, meaning that these hydrogen bond are perpendicular to the axis of the helix (whereas the H-bonds in an alpha-helix are parallel to the axis of the helix)
II. Structure of collagen - Secondary structure of collagen
8. The assembled collagen superhelix has a tiny core/hole in the middle of it
=> What is the feature of this hole?
The assembled collagen superhelix has a tiny core/hole in the middle of it, which is so small that only a single proton (H+) can fit into it = glycine side chain
II. Structure of collagen - Secondary structure of collagen
9. Why must every 3rd AA be glycine in a collagen superhelix?
- The assembled collagen superhelix has a tiny core/hole in the middle of it, which is so small that only a single proton (H+) can fit into it = glycine side chain
- This is why every 3rd AA must be glycine, because each 3rd AA would face the core of the collagen superhelix, and only glycine’s side chain can fit in this tiny hole
III. Collagen synthesis
1. What are the steps of collagen synthesis?
- Collagen is initially synthesized as the large precursor polypeptide: procollagen
- Procollagen contains 3 collagen peptides, forming a collagen superhelix with a globular C- and N-terminal that are not part of the superhelix (help in folding)
- The globular terminal domains are cleaved by a procollagen peptidase to form tropocollagen, which then only consists of a collagen superhelix
- The tropocollagen is the collagen monomer => tropocollagens assemble parallelly to each other forming a collagen fiber. They are ‘’slided’’ relative to each other so that they do not start/stop at the same place (would make the structure unstable)
III. Collagen synthesis
2. What are the features of procollagen?
- Collagen is initially synthesized as the large precursor polypeptide: procollagen
- Procollagen contains 3 collagen peptides, forming a collagen superhelix with a globular C- and N-terminal that are not part of the superhelix (help in folding)
- The globular domain functions in holding the superhelix together, stabilizing the inter-chain H-bonds:
+) N-terminal: forms alpha-helices that aid in formation of the triple helix
+) C-terminal: prevents unfolding of the newly formed collagen triple helix
III. Collagen synthesis
3. How is tropocollagen formed?
The globular terminal domains are cleaved by a procollagen peptidase to form tropocollagen, which then only consists of a collagen superhelix
III. Collagen synthesis
4. What are the features of tropocollagen?
- The tropocollagen is the collagen monomer
=> tropocollagens assemble parallelly to each other forming a collagen fiber. - They are ‘’slided’’ relative to each other so that they do not start/stop at the same place (would make the structure unstable)
III. Collagen synthesis
5. There are small holes between successive tropocollagen monomers
=> Why do we need to have these holes?
The small holes between successive tropocollagen monomers can be filled by various materials that cause differentiation into different types of tissue:
- Hydroxyapatite: differentiate into bones
- Polysaccharides: differentiate into skin/tendons
IV. Hydroxylation of collagen
1. What are the features of collagen hydroxylation?
Hydroxylation of collagen is responsible for the conversion of proline -> hydroxyproline
- Enzyme: prolyl hydroxylase
- Requires: O2, alpha ketoglutarate, Fe2+, ascorbic acid
- Formation of 4-hydroxyproline + CO2, H2O2, succinate
IV. Hydroxylation of collagen
2. What happen if there is ascorbic acid deficiency (vitamin C) such as in scurvy?
- In ascorbic acid deficiency (vitamin C) such as in scurvy -> the CT becomes loose, because without hydroxyproline, the CT loses its integrity.
- The hydroxylation alters the melting point (stability) of the collagen helix. The melting point of collagen is always just above the body temperature:
+) No hydroxylation = melting
+) Too much hydroxylation = too rigid - Collagen ‘’needs’’ to be unstable = close to melting point, so that it can be rearranged when needed (remodeling) -> this is regulated by the level of hydroxylation
V. Aging of collagen fibers
1. Describe aging of collagen fibers
- Collagen ageing occurs due to oxidation-induced crosslinks between the triple helices
- Oxidation is the major reason for aging, due to the accumulation/increased production of reactive oxygen species (ROS)
- ROS can create crosslinks between tropocollagen monomers, making them more rigid.
- Increased rigidity = reduced elasticity -> the reason why elder people break bones more easily (bone is less elastic -> more vulnerable)
VI. Pathobiochemistry of collagen
1. Give 2 examples of metabolic disorders related to collagen
- Scurvy
- Menkes syndrome
VI. Pathobiochemistry of collagen
2. What are the features of Scurvy?
VI. Pathobiochemistry of collagen
3. What are the features of Menkes syndrome?
VI. Pathobiochemistry of collagen
4. Give 2 examples of genetic disorders related to collagen
- Ehlers-Danlos syndrome
- Osteogenesis imperfecta
VI. Pathobiochemistry of collagen
5. What are the features of Ehlers-Danlos syndrome?
VI. Pathobiochemistry of collagen
6. What are the features of Osteogenesis imperfecta?
