Tertiary and quaternary structure and haemoglobin

Non-covalent bonds

• Hydrogen bonds

• Ionic bonds

• Van-der waals forces

• Hydrophobic effect

Covalent bonds

• Disulphide bridges

Hydrogen bonds

• Between peptide bonds in 2* structure

• Between polar R groups in 3* and 4* structure

Ionic bonds

• Aka salt bridges

• Between charged R groups in 3* and 4* structure

Van der Waals

• Between non-polar charged R groups in 3* and 4* structure

Hydrophobic effect

• In 3* and 4* structure

Disulphide bridges

• Between cysteine R groups in 3* structure

Describe properties of cysteine

• Disulphide bridges between 2 cysteine residues

  • In proteins that have to withstand harsh environments

Explain the thermodynamics of protein folding

• ^G=^H-(T^S)

• ^H is negative = favours folding of proteins

• ^S is negative = favours unfolding (unordered state) over folding (ordered state)

• ^G = -40kJmol ===> proteins are easily destabilised by mutations/environment changes

Outline the importance of the anfinsen project

• Showed that protein sequences contains info needed for it to fold

Give examples of post-translational modification

• Phosphorylation

• Methylation

• Acetylation

• Glycolysation

Explain physiological features of myoglobin

• I muscle

• Short term oxygen storage

• 1 polypeptide chain

• 1 haem group = 1 oxygen

Describe physiological roles of haemoglobin

• In blood

• Transports oxygen

• 4 polypeptide chains

• 4 haem groups = 4 oxygen

Does Haemoglobin or myoglobin have a greater affinity for oxygen

Myoglobin

Explain the allosteric nature of haemoglobin

Allosteric = 2 different forms

• T state = low affinity

• R state = high affinity

  • Conformational change depending on binding of oxygen

Describe examples of allosteric regulators

• Negative allosteric regulators (inhibitors) = stabilise T state (low affinity)

• Positive allosteric regulators (activators) = stabilise R state (high affinity)

• BPG = binding of BPG to haemoglobin lowers affinity of haemoglobin for oxygen (inhibitor)

• Carbon dioxide/H+ = lowers affinity for oxygen

  • Oxygen is delivered to metabolically active tissue

Explain how mutations lead to sickle cell

• Point mutation

  • GAG —> GTG

• Glutamate to Valine

  • Val is hydrophobic

• So the molecule lies in the T state