MGD S2 - Protein Structure Flashcards
Define primary structure (protein)
The amino acid sequence of a protein
Define secondary structure
- Stretches of a polypeptide chain that forms α-helices and β-sheets
- Bonds on either side of the peptide bond can rotate freely
Define tertiary structure
The full 3D structure of the protein. Involves the folding up of the secondary structures. Improper folding (amyloidosis) may cause disease. Most proteins fold spontaneously, but some require the help of molecular chaperones
Define quaternary structure
Interaction between the arrangement of different polypeptide chains (subunits) within the same proteins. The polypeptide chains may be identical (homomeric) or different (heteromeric)
Describe the types of bonds and forced involved in protein structure
Primary - Covalent (peptide) bonds
Secondary - Hydrogen bonds
Tertiary - Hydrogen bonds/ Van Der Waals/ Hydrophobic Interactions/Covalent (disulphide)/ionic interactions
Quaternary - Same as tertiary
Explain the physiological role of myoglobin
A single subunit protein that contains one Haem group for the binding and transport of oxygen. It can bind one molecule of oxygen. Mb exhibits hyperbolic oxygen binding - not cooperatively
Explain the physiological role of haemoglobin
A tetrameric protein (2α and 2β subunits) containing haem groups. It can bind 4 molecules of oxygen Hb exhibits sigmoidal oxygen binding - Cooperative binding
Contrast the oxygen binding abilities of haemoglobin and myoglobin
Mb has a very high affinity for O2, thus will only release O2 when pO2 is extremely low.
Hb however can exist in two states:
1) A low affinity T-state (tense)
2) High affinity R-state (relaxed).
Transition between these two states give Hb it’s sigmoidal binding curve
- Hb’s affinity to O2 increases as more O2 binds, co-operative binding.
What effect does 2,3-bisphosphogylcerate (2,3-BPG) have on haemoglobin?
- Decreases the affinity of HB for oxygen
- Curve shifts to the right
- 2,3 BPG concentration increases at high altitudes, promoting oxygen release
- 2,3 BPG also produced during metabolism, so oxygen is released more readily in areas performing high amounts of metabolism
What effect does Carbon dioxide and H+ have on haemoglobin affinity for oxygen?
Bohr effect - decreased affinity at sites of low pH and increased carbon dioxide, for example muscles during exercise, more oxygen is required and will be released
What effect does carbon monoxide have on haemoglobin?
Binds to haemoglobin 250 times more readily than oxygen. It is fatal when COHb is greater than 50% The binding of CO also acts to increase the affinity of unaffected subunits for oxygen
What is the bases change in sickle cell anaemia?
Adenine to Thymine
What is the amino acid change in sickle cell anaemia?
glutamate (hydrophilic) to valine (hydrophobic)
Describe how the change in amino acids in sickle cells anaemia brings about its pathophysiology
The change form glutamate to valine forms a ‘sticky hydrophobic pocket’ formed by valine allows deoxygenated Hb’s to polymerise. This leads to the distortion of red blood cells into the sickle cell shape. This distortion causes stress to the cell membrane and causes premature lysis (normal RBC = 120 days, SCA RBC = 30days) The sickle cell shape also block microvasculature
Describe the pathophysiology of thalassemias
A group of genetic disorders where there is an imbalance between α and β subunits
Where is myoglobin found ?
Muscles (all tissue)
Name the dissociation curve produced by myoglobin
Hyperbolic
What are the components of haem?
- 4 nitrogen atoms
- 1 central Fe atom
How is Fe atom bonded to haemoglobin?
Bound to protein via histidine on the other side of the ring
List the features of haemoglobin structure
- 4 polypeptide chains
- 2 alpha, 2 beta chains forming a tetramer
- 4 Haem groups
Define the two states of haemoglobin
T state- low affinity for oxygen
R state- high affinity oxygen
What conformational change occurs when oxygen binds to haemoglobin or myoglobin?
Fe in deoxygenated molecule is slightly below the plane of the ring. Oxygen binding causes movement of Fe up into the plane of the ring leading to a small change in the overall protein conformation
Why is alpha thalassemia onset before birth whereas beta is after birth?
Alpha thalassemia is a deficiency of alpha chains whereas beta is a deficiency of beta chains In foetal haemoglobin, gamma chains are present which can bind to alpha chains to form stable tetramers until beta chains develop after birth. In the absence of alpha chains, stable tetramers cannot form.
What is the difference between foetal and adult haemoglobin?
Foetal haemoglobin contains gamma chains opposed to beta and has a higher affinity for oxygen than adult haemoglobin to ensure the transfer of O2 into the foetal blood supply from the mothers. Approximately less than 2% of HbF is retained in adult RBCs.
