Bonev - Structural proteins Flashcards
What are some characteristics found in structural proteins and not found in globular proteins?
- Long, filamentous
- Insoluble
- Contain unusual amino acids
- Often contain cross-linked polypeptide chains (polypeptides are covalently linked together to give a more stable structure)
What happens to keratin when epithelial cells die?
Keratin is retained within the cells and produced
Where is a-keratin predominantly found?
Outermost layer of skin, horns, hooves, and hair
Where are b-keratins found?
Feathers, scales
What type of structure does keratin form?
Forms alpha helical structures in a right-handed way
Which way does it supercoil though?
Left-handed. Right-hand coils supercoil in a left-hand sense.
How many residues are present per turn in the protofilaments?
Two coiled right-hand helices with 3.5 residues per turn. Alpha helix has 3.6 residues per turn.
What is the pitch?
0.51nm
What is the pitch for the LH supercoiling?
21nm
8 protofibrils form a keratin microfilament. Cysteine can also form disulfide bonds with other cysteine molecules which stabilises the entire structure.
What type of helical wheel is present in the keratin structure?
Heptad helical wheel
Why is it important that Leu, Ile, Ala are found at ‘a’ and ‘d’?
These are hydrophobic causing a hydrophobic surface, allowing interaction between the two coils, making it more stable
What happens if Arg and Lys (both positive) are found at opposite positions of the heptad wheel (at g and e)?
They will form a salt bridge with negative residues to stabilise the elctrostatic interactions
Where is collagen found?
In connective tissue like bones, cartilage, ligaments, tendons, and skin
Which amino acid comprises 33% of collagen?
Glycine
Why is tryptophan not found in collagen?
Because it has bulky sidechains which would disrupt the tight packaging and stability of the tight triple helix
How many amino acids make each of the three chains in collagen?
1000 amino acids
What handedness are they each?
Right-handed
They are 300nm long, 1.4nm in diameter, 285kDa in molecular weight
Why does collagen have proline present in its structure?
Because it is unable to form hydrogen bonds
Why does collagen not want hydrogen bonding as much as other structures?
Because a reduced amount of hydrogen bonding leads to increased flexibility
Which amino acid is present in collagen so that there is some hydrogen bonding for stability?
Hydroxyproline
How does hydroxyproline work?
It serves as a hydrogen bond acceptor and raises the melting temperature from 24ºC to 40-60ºC
Helical pitch is around 0.95nm with 3.3 residues per turn
Why is it important to have glycine in the structure?
It faces inwards and has no sidechains. This gives it a more tight and compact structure.
What is the difference between collagen and tropocollagen?
Tropocollagen is each of the individual strands but collagen is the three strands together
What is the higher order of organisation present in tropocollagen? (staggering)
Staggered alignment of tropocollagen, 64nm staggering with 40nm gaps
There is some covalent cross-linking within individual helices, as well as between helices
An allysine and lysine can react together to form what?
Schiff base with no chemically active group
Why is hydroxylation of lysine and proline needed as a post-translational modification in collagen formation?
To enable the possibility of hydrogen bonding to increase stability like the melting point increasing
Why is glycosylation needed?
Serine for example needs to be glycosylated to make it more soluble and facilitate exocytosis
Which amino acids make up collagen?
Glycine, proline, alanine, hydroxyproline, and others
Where does a mutation tend to occur in collagen?
Glycine
What does this lead to?
Collagen misfolding, increased Lys hydroxylation, improper processing of the protofilaments by enzymes and chaperones, and weakening of the collagen protofilaments
Where is elastin found?
Connective tissue like arterial walls and ligaments
What is it mainly composed of?
Gly 33%, 22% Ala, 14% Val, 11% Pro
How can elastin form a mesh-like structure to make it more stable and compact?
Lysine has its sidechains form isodesmosine and desmosine. These enable flexibility and strength in these covalent structures.
Fibrillin is found in microfibrils which contribute alongside elastin and collagen to the structure of the extracellular matrix. What is unique about fibrillins?
They have 47 Epidermal Growth Factors, 43 of which bind to calcium
What is Marfan’s syndrome a result of and what does this prevent?
Mutations found in the Epidermal Growth Factors and this reduces calcium binding
What does this lead to?
Extensive growth of organism, extended vasculature
Where is fibroin secreted from?
Insects and arachnids
What is the amino acid content?
Gly 45%, Ala 30%
What is the main secondary structure found in fibroin?
Antiparallel beta sheets
They have lots of glycine so there are no side chains. The sheets can slide against each other which makes it very flexible. It is an exceptionally strong polymer.
If all these sheets come together, what type of structure is formed?
Crystalline domains
Polyalanine motifs are repeated throughout the structure, what does this give it?
A lot of strength and rigidity
What holds this crystalline structure together?
Sericins
Which enzyme converts lysine to allysine in collagen?
Lysyl oxidase
What is the purpose of allysine being produced in collagen?
It can form cross-bridges with other allysine which stabilises the structure further
Which Schiff base is produced when allysine reacts with a lysine?
Lysinonorleucine
Why is this important in collagen?
Provides structural stability
