28-09-21 - Structure of Proteins 2 Flashcards
What is tertiary folding of a protein?
What does it consist of?
What affects how the protein is folded? => POLAR/ NON POLAR
How is the protein organised?
What are examples of these organised sections?
- Tertiary structure is the 3D folding of secondary structure into a globular structure
- Tertiary structure consists of loops/bends connecting regions of alpha helices and beta-sheets so the polypeptide can fold into a globular structure
- There can be alpha helices, beta sheets, or a mix of both (more common)
- The hydrophobic residues are buried and the hydrophilic residues are exposed to the aqueous environment, which affects how the protein is folded.
- Many proteins are organised into multiple domains, with each domain contributing a specific function to the overall protein.
- Domains may be kinases (enzymes, cysteine-rich, globin- domains etc.
What are intermolecular and intramolecular bonds that stabilise tertiary structure?
What do they consist of?
What do they contribute to? <=> stability
- Intramolecular
- Disulphide bones (disulphide bridges) – covalent bonds that form between two sulphur atoms from separate cysteine residues – found in Bovine Serum Albumen (17 bridges)
- Ionic interactions – formed between positively and negatively charged residues
- Intermolecular
- Hydrogen bonds – Form between H and F, N, or O of another residue, but only if the H is bonded to an F, N, or O
- Hydrophobic interactions – forms between hydrophobic side chains
- Van der Waals interactions
- These bonds contribute to the lowest energy of the state = most stable from of the protein which governs its tertiary structure.
When is Quaternary structure present in proteins?
What are these proteins referred to as? OLIBOLI
How is the quaternary structure stabilised?
What are some examples of proteins with quaternary structure?
Mechanosensitive conductance channel – ion channel that responds to movement –
Stored insulin –
Heterotrimeric G protein –
70S Ribosome
- Quaternary structure is present in proteins that consist of several polypeptide chain subunits
- Proteins consisting of several subunits are known as oligomeric proteins
- These subunits (monomers) can be identical or different.
- Disulphide bonds often stabilise the oligomeric structure.
- Mechanosensitive conductance channel – ion channel that responds to movement – 7 identical subunits
- Stored insulin – 6 identical subunits bound to Zinc
- Heterotrimeric G protein – 3 different subunits – alpha, beta, gamma
- 70S Ribosome – 30different subunits
What is haemoglobin for?
What does it consist of?
What does each subunit contain and why?
- Haemoglobin carries oxygen in red blood cells.
- It is an asymmetrical assembly of 4 subunits (2 alpha globin chains and 2 beta globin chains)
- Each of the subunits contains a haem molecule, which binds oxygen for transport to the tissues.
What does a haem molecule consist of?
How are they held in place in the globin chain and stabilised?
- Haem consists of a porphyrin ring with an Fe2+ ion in the centre, which is used for binding oxygen
- Each haem molecule is held in place by hydrogen bonds from the histidine F8
- When haem is oxygenated, it is stabilised by Histidine E7.
What is cooperative binding?
How does it occur?
NON PLANAR/ PLANAR
What does cooperative binding cause on a graph?
- Co-operative binding is when the initial affinity for binding oxygen in haemoglobin is low, but the binding of oxygen to one subunit causes an increase in affinity for binding oxygen in the remaining 3 subunits.
- This is due to a change in protein structure as the first oxygen molecule binds, resulting in a change of the molecule shape from non-planar to planar
- When the first oxygen molecule binds, the histidine f8 that hydrogen bonds to the haem molecule changes position.
- This causes major structural realignments elsewhere in the molecule, leading to a dramatic increase in affinity for binding oxygen in the remain free subunits.
- Cooperative bind results in the sigmoidal oxygen binding curve.
What is the biological significance of cooperative binding?
=> lungs/ tissues
- Cooperative binding means small changes in oxygen concentration will cause large changes in the interaction between haemoglobin and oxygen
- This results in tight oxygen binding in the lungs where oxygen concentration is high, and subsequent release in tissues where oxygen concentration is lower.
How is sickle cell anaemia caused?
hydrophiliv vs phobic
How does it affect the red blood cell?
What effects does it have on the red blood cell?
- Sickle cell anaemia is caused by a single amino acid change on position 6 of the beta chains of haemoglobin
- The change is from the hydrophilic glutamic acid to the hydrophobic valine.
- This results in hydrophobic areas of the beta chains being exposed to the aqueous environment
- This causes the haemoglobins to aggregate (cluster), which forms a stiff fibre.
- This causes the red blood cells to have a sickled shape, making it harder for them to fit through thin blood vessels like capillaries.
- It also greatly reduces their ability to carry oxygen
What is the Bohr effect?
How does pH affect haemoglobins binding of oxygen?
What is the significance of this?
How is delivery of oxygen sped up during exercise?
- Bohr effect – the pH of the blood influences O2 binding to haemoglobin
- O2 binding occurs with higher affinity at high pH (lungs) and lower affinity at low pH peripheral tissues.
- O2 loading is therefore easier in the lungs and unloading occurs faster in the tissues where oxygen is needed.
- CO2 (acidic) builds up during exercise, which makes the environment more acidic
- This lowers the pH in tissues further, which makes oxygen delivery faster.
How does foetal haemoglobin vary from regular haemoglobin?
What is the significance of this?
How does this affect those who suffer from sickle-cell anaemia?
- Normal haemoglobin consists of 2 alpha and 2 beta globin chains
- Foetal haemoglobin consists of 2 alpha and 2 gamma globin chains
- The oxygen dissociation curve for foetal haemoglobin is left shifted from adult haemoglobin
- This is because there is a low O2% by the time the blood reaches the placenta, so the haemoglobin needs to bind with greater affinity to oxygen.
- This also means that foetuses are unaffected by sickle cell-anaemia, as they have no beta globin chains.
What is collagen?
What is it used for?
Where is it found?
What is its structure like?
- Collagen is a protein that makes up around 25% of the total protein mass in the body.
- It is the chief protein in bone, tendon and skin and helps bind cells together to form tissues
- It is assembled in long, extremely strong fibres.
What are the building blocks of collagen fibres?
- Tropocollagen is the building block of collagen fibres
- Many Tropocollagen helices form a microfibril. Many microfibrils form a fibril. Many fibrils form a collagen fibre.
What do tropocollagens consist of? Why is it structured like this? What amino acids allow it to be structured like this? How does the structure of tropocollagens differ from alpha helices?
Sure! Here’s a simpler breakdown:
- Tropocollagen Structure: Tropocollagen is made up of three polypeptide chains that twist together to form a tight structure known as a triple helix. The twist is a mix of left-handed (individual chains) and right-handed (the overall helix) turns.
- Role of Proline: Proline, an amino acid, helps create bends or “kinks” in the chains, which allows for this unique twisting. Some prolines can also change into hydroxyproline, which helps stabilize the structure by forming hydrogen bonds.
- Importance of Glycine: Glycine is another amino acid that is crucial in this structure; it appears every third position in the chain. Because it has a very small side chain, it helps the chains pack closely together and supports the right-handed twist.
- Helix Types: The tropocollagen helices twist in a left-handed manner and have three amino acids in each complete turn, making them tighter. In contrast, alpha helices (another type of helix found in proteins) twist in a right-handed manner and have 3.6 amino acids per turn, making them looser.
Overall, the combination of these amino acids and their unique arrangements creates a strong and stable protein structure!
How are collagen fibres formed by tropocollagens?
What helps to stabilise the structure?
- Tropocollagen molecules are assembled adjacent to each other in a quarter-stagger model
- This stagger provides stability.
- The gaps between the tropocollagens provide access sites for the enzyme lysyl oxidase
- Lysyl oxidase initiates covalent cross-links between the tropocollagen molecules, which involve lysine-derived aldehydes.
- These covalent cross-links stabilise the tropocollagen structure and the collagen fibre.
What is Osteogenesis imperfecta?
What is it caused by? + mutation effect
What are signs of this? the eyes chico
- Osteogenesis imperfecta is a form of brittle bone disease.
- It is caused by a mutation in the gene coding for one of the collagen subunits, leading to a glycine being replace by cysteine reside at some point in the chain
- At this point in the mutation, there is a loss of the triple helix structure in tropocollagen.
- This prevents tropocollagen subunits from binding tightly together, which has a knock-on effect on collagen fibre formation.
- Choroidal veins in the eyes are exposed due to defective collagen formation.
What are the 3-collagen related diseased?
What are symptoms?
How are they caused?
osteogenesis perfecta
scurvy
ehlers danloss syndrome
- Procollagen peptidase – cleaves loose ends off of tropocollagen sub-units
What are the examples of strength built in at all levels of the collagen fibre?
close packing of subunits
oppoaing twists of subunits and superhelix
hydrogen bonding
cross linking
