Tertiary + Quaternary Structure Flashcards
How do proteins fold?
- Loops = connect alpha helices + beta sheets due to hydrophilic amino acids
- Turns
- Non-covalent bonding
- SOME covalent forces
What is a motif?
SECONDARY structures together
- Can be a helix-loop-helix or a β-α-β
What is a domain?
Many motifs that fold to give a stable TERTIARY STRUCTURE
What is a subunit?
Combination of many domains
- 2 Subunits form a QUARTNERARY structure
What forces hold TERTIARY structures together?
- Covalent BONDS (disulfide)
- Weak FORCES
- H bonds
- Hydrophobic bonding (due to H2O trying to maximise H bonding)
- London (Van der Waals/Dispersion) Forces
- Electrostatic (ionic + dipole-dipole)
How do you calculate the size of an electrostatic force?
E = (Z+ x Z-) / D x r2
where Z is the charge on + and - centre
D is the dielectric constant (depends on solvent)
and r is the distance squared
What are the 2 STRONG interactions?
Covalent bonds + Ionic Bonds
What are the 3 WEAK interactions?
H-bonds
London Forces
Hydrophobic interactions
How do TERTIARY conformations form?
- Collapse into hydrophobic interactions
(favour contact between the aliphatic R groups) - Hydrophilic R groups expose to solvent
∴ protein structure fluctuates until interactions are optimum
∴ H and disulphide bonds can form
What are TERTIARY structures largely determined by?
The overall sequence of amino acids and weak interactions between the side chains
What is packed in the internal core of a TERTIARY structure?
Aliphatic + Hydrophobic groups
Why does H2O binding to the exposed polar sides form a hydration shell?
hydrophobic groups bury inside
∴ increased entropy of H2O
What protein structure does myoglobin have?
TERTIARY
What protein structure does haemoglobin have?
QUARTENRNARY
Where is myoglobin found?
Skeletal muscle
What does myoglobin store?
O2 storage protein
What size in Å is myoglobin?
45x35x25 Å
What are 78% of the alpha helices linked by in myoglobin?
Turns
no beta sheets
Why is there an empty space in myoglobin?
Hydrophobic amino acids packed inside
Why is histidine essential in the binding site of myoglobin?
Histidine:
- hosts the haem
- stop the oxidation to the Ferric form
- provide an O2 binding site
Haem has 2 residues:
- Distal Histidine
- Proximal Histidine
Where is haemoglobin found?
In erythrocytes (red blood cells)
What does haemoglobin do?
Carries O2 around the body
How many subunits are there in Hb?
4 = tetramer
- Each has a haem group
- 2 diff. types: alpha + beta which differ in sequence
What length in Å are the haem groups separated by in Hb?
24 - 40 Å from Fe to Fe
How similar is each chain of Hb to myoglobin?
Around 24% similar
- Proximal + Distal Histidines retained = KEY RESIDUES
Between Hb and myoglobin, which protein has a lower affinity (binds less easily) for O2?
Haemoglobin
- Myoglobin is a monomer not a tetramer so has no significant affinity for BPG
What happens to Hb when an oxygen binds?
Each subunit rotates by 15° and move by 0.8Å, making it easier for the next oxygen to bind
Between Hb and myoglobin, which protein binds more strongly for any pO2?
Myoglobin
What happens to Hb in the lungs?
Hb saturated DUE TO HIGH pO2
What happens to Hb in the tissues?
Hb unsaturated DUE TO LOW pO2
- Delivers only 66% of bound O2 due to non-cooperative binding
What is ligand BPG?
allosteric effector
- lowers affinity of O2
∴ Hb binds more strongly
Where does BPG bind on Hb?
Central cavity of subunits
Why does BPG only bind to Hb in the deoxygenatedHb state?
BPG is released when O2 binds
What does BPG do?
- BPG controls O2 binding
- BPG stabilises deoxygenated Hb (weakening O2 binding)
Is foetal Hb or maternal Hb affinity for O2 higher (binds more easily)?
Foetal is higher as it doesn’t bind as well to BPG, therefore gets O2 from the mother
What other allosteric effector is there?
CO2
- Concentration affects O2 binding properties (Bohr Effect)
