Flashcards in Fibrous Proteins_Molecules Deck (38):
What are the properties of fibrous proteins?
1) Low solubility
2) No tertiary structure/ no quaternary structure especially collagen, elastin, keratin
3) Mechanical strength/flexibility
4) long chains
6) Cross links: covalent cross links to hold them together
Name the keratin diseases
1) Epidermolysis bullosa simplex
2) Junctional epidermolysis bullosa
3) Dystrophic epidermolysis bullosa
What is epidermolysis bullies simplex?
- Form of epidermolysis bulls that causes blisters at the site of rubbing
- Autosomal dominant
- Affects keratin genes
What is junctional epidermolysis bullosa?
- Inherited disease affecting lamina and collagen
- blister formation within the lamina lucida of the basement membrane zone
- Autosomal recessive
- Blisters at the site of friction
What is dystrophic epidermolysis bulls?
- Inherited variant affecting the skin and other organs
- Skin very fragile
- Cause by genetic defect (or mutation) within the human gene encoding protein type VII collagen
- Autosomal dominant or autosomal recessive
What does keratin do?
1) Give structural support to epithelial cells
2) Keratin cytoskeleton of dead cells forms hairs, fingernails and the horny layer of skin
Keratin is under what class?
One of the several classes of intermediate filaments
What do all keratins contain?
Long stretches of alpha helix interrupted by non helical segments.
What are the two different types of keratin?
1) Acidic (Type 1)
2) Basic (Type 2)
What do they form with type 1 polypeptides?
What do they form with type 2 polypeptides?
A coiled coil
How do alpha helices of the two keratins make contact?
through hydrophobic AA side chains on one edge of each helix.
What is the structure of keratin
- Protein chains twist in pairs
- Left handed superhelix "coiled coil"
- Hydrophobic faces (facing each other)
- S - S cross links
Can the S - S cross links be chemically undone?
- If it is not there anymore, keratin becomes more flexible
- Adding hydrogen at a warm temperature (using hot water) reduces disulphide bridge
What happens to keratin fibres in a high oxidising environment?
H can be removed, allowing covalent links to join keratin fibres by disulphide bond
Why is keratin a left handed superhelix
- Pair of twisted alpha helices
- Strongest way is to turn it in the opposite way of the primary helix
What type of cross links happen in collagen?
- H bonds (HyPro) - forms cross links by H bonds
- Covalent (Lysinorleucine) - pairs of lysine forms covalent bonds
Name the collagen disease
- Scurvy: vitamin C
- Ehlers - Danlos syndrom
- Osteogenesis Imperfecta
Most mammals make vitamin C except which mammals?
Humans and Guinea pigs
What happens to sailors and Arctic explorers?
Collagen falls apart
How many human collagen genes can be affected to cause a collagen disease?
19 human collagen genes
What happens in Ehlers-Danlos syndrome?
- Weak connective tissue
- Especially Glycine -> X mutations
- Lethal: fatal in womb
- Minor: Double jointed
What happens in osteogenesis imperfect?
- Brittle bones/deformity
- Shortened collagen chains (deletions)
- Sever: Fatal before birth
Name the most abundant fibres in strong, tough connective tissue.
In which connective tissue, is collagen present in?
What is a characteristic of type 1 collagen?
Most unusual amino acid composition
- 35% Glycine
- 21% Proline and hydroxyproline
- 11% Alanine
- 0.6% Hydroxylysine
What does hydroxproline need?
Need vitamin C
How is glycoprotein made?
Carbohydrate attached at Hydroxylysine
What is inorganic bone matrix made of?
What percentage of bone and skin is made of collagen
1/4 bone: Collagen
3/4 skin: Collagen
Hydroxylated AA are not represented in the genetic code, therefore...?
Therefore they must be synthesised post translationally from prolyl and lysyl residues in the polypeptide
How are collagen chains made?
Three intertwined polypeptide chains in a superhelix
What is the unusual polypeptide AA sequence that collagen chains have?
Have glycine in every third position - all glycine residues are on the same side of the helix
What are the properties of a collagen helix (one collagen chain)?
- Left handed helix (NOT ALPHA)
- 3 residues/turn
- no H bonds
- held together by steric repulsion of the bulky proline and hydroxyproline side chains
What forms the collagen superhelix?
3 left handed helix is turned around in a right handed manner to form the superhelix
How is the collagen superhelix superficial structure held together?
By hydrogen bonds between the peptide bonds of the interacting polypeptides
How is glycine faced in the collagen superhelix?
Glycine is faced each other in the center of the superhelix.