MGD S2 - Protein Structure

Question 1

Define primary structure (protein)

Answer 1

The amino acid sequence of a protein

Question 2

Define secondary structure

Answer 2

• Stretches of a polypeptide chain that forms α-helices and β-sheets
• Bonds on either side of the peptide bond can rotate freely

Question 3

Define tertiary structure

Answer 3

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

Question 4

Define quaternary structure

Answer 4

Interaction between the arrangement of different polypeptide chains (subunits) within the same proteins. The polypeptide chains may be identical (homomeric) or different (heteromeric)

Question 5

Describe the types of bonds and forced involved in protein structure

Answer 5

Primary - Covalent (peptide) bonds

Secondary - Hydrogen bonds

Tertiary - Hydrogen bonds/ Van Der Waals/ Hydrophobic Interactions/Covalent (disulphide)/ionic interactions

Quaternary - Same as tertiary

Question 6

Explain the physiological role of myoglobin

Answer 6

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

Question 7

Explain the physiological role of haemoglobin

Answer 7

A tetrameric protein (2α and 2β subunits) containing haem groups. It can bind 4 molecules of oxygen Hb exhibits sigmoidal oxygen binding - Cooperative binding

Question 8

Contrast the oxygen binding abilities of haemoglobin and myoglobin

Answer 8

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.

Question 9

What effect does 2,3-bisphosphogylcerate (2,3-BPG) have on haemoglobin?

Answer 9

• 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

Question 10

What effect does Carbon dioxide and H+ have on haemoglobin affinity for oxygen?

Answer 10

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

Question 11

What effect does carbon monoxide have on haemoglobin?

Answer 11

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

Question 12

What is the bases change in sickle cell anaemia?

Answer 12

Adenine to Thymine

Question 13

What is the amino acid change in sickle cell anaemia?

Answer 13

glutamate (hydrophilic) to valine (hydrophobic)

Question 14

Describe how the change in amino acids in sickle cells anaemia brings about its pathophysiology

Answer 14

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

Question 15

Describe the pathophysiology of thalassemias

Answer 15

A group of genetic disorders where there is an imbalance between α and β subunits

Question 16

Where is myoglobin found ?

Answer 16

Muscles (all tissue)

Question 17

Name the dissociation curve produced by myoglobin

Answer 17

Hyperbolic

Question 18

What are the components of haem?

Answer 18

• 4 nitrogen atoms
• 1 central Fe atom

Question 19

How is Fe atom bonded to haemoglobin?

Answer 19

Bound to protein via histidine on the other side of the ring

Question 20

List the features of haemoglobin structure

Answer 20

• 4 polypeptide chains
• 2 alpha, 2 beta chains forming a tetramer
• 4 Haem groups

Question 21

Define the two states of haemoglobin

Answer 21

T state- low affinity for oxygen

R state- high affinity oxygen

Question 22

What conformational change occurs when oxygen binds to haemoglobin or myoglobin?

Answer 22

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

Question 23

Why is alpha thalassemia onset before birth whereas beta is after birth?

Answer 23

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.

Question 24

What is the difference between foetal and adult haemoglobin?

Answer 24

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.