3D structure of protein

Question 1

What does the folding of a protein depend on? [3 marks]

Answer 1

• The amino acid sequence.
• The molecular structure and properties of its amino acids.
• The molecular environment (solvent & salt).

Question 2

What is the isoelectric point? [1 mark]

Answer 2

The pH value at which a zwitterion has an equal number of positive and negative charge.

Question 3

What properties do glycine have? [1 mark]

Answer 3

Properties that reduce steric hindrance (slowing of chemical reactions due to steric bulk).

Question 4

Where is polarity located on polar amino acids? [1 mark]

Answer 4

At either side of the peptide bond.

Question 5

What is the difference between charge amino acids and polar amino acids? [2 marks]

Answer 5

• They don’t carry the charge in the same way.

- Polar amino acids have a dipole.

Question 6

What conformation is the variable side chain is? [1 mark]

Answer 6

Trans

Question 7

Why is the peptide bond ridged? [1 mark]

Answer 7

• The delocalised electrons of the NH3-COOH.

- The O2 and H2 atoms are on opposite sides and lying in the same plane.

Question 8

What do the delocalised electrons do to the peptide bond? [1 mark]

Answer 8

It causes the bond to act like a double bond and restricts movement.

Question 9

Where is there rotational freedom on the polypeptide chain? [1 mark]

Answer 9

Around the alpha carbon (it allows a huge variation in the confirmation of the polypeptide chain).

Question 10

Which bonds allow the polypeptide to fold? [2 marks]

Answer 10

• C-Cα (psi bond)

- Na-Cα (phi bond)

Question 11

What determines the most favourable arrangement of atoms? [1 mark]

Answer 11

The minimisation of free energy (G).

Question 12

What is free energy of a confirmation affected by? [3 marks]

Answer 12

• Aqueous or lipid membrane
• Other proteins or molecules (including salts and ionic states)
• Changes in the environment (e.g. a receptor binding a ligand)

Question 13

What are the non-covalent bonds in proteins? [4 marks]

Answer 13

• Electrostatic attractions
• Hydrogen bonds
• Van der Waals attraction (dipoles)
• Hydrophobic interaction

Question 14

Where do disulphide bonds occur? [1 mark]

Answer 14

Cysteine

Question 15

What are the two types of beta sheets/turns? [2 marks]

Answer 15

• Antiparallel: N-terminus of one strand is adjacent to the C-terminus of the next.
• Parallel: N-termini of successive strands are oriented in the same direction.

Question 16

Which diseases result from misfolded proteins? [6 marks]

Answer 16

• Huntington’s (Huntingtin)
• Alzheimer’s (Amyloid-beta)
• Parkinson’s disease (Alpha-synuclein)
• Type 2 diabetes (Islet amyloid polypeptide)
• PrPSc (Prion proteins)
• AA amyloidosis (Serum amyloid A)

Question 17

What can mis-folding be caused by? [6 marks]

Answer 17

• Somatic mutations.
• Errors in transcription or translation.
• Failure of the folding machinery.
• Mistakes of the post-translational modification or in trafficking in proteins.
• Structural modification via environmental changes.
• Induction protein mis-folding by seeding and cross seeding by other proteins.

Question 18

What is seeding? [1 mark]

Answer 18

When a normal protein is exposed to a protein in a disease-causing confirmation and that normal protein becomes mis-folded.

Question 19

What causes Alzheimer’s? [3 marks]

Answer 19

• Unusual proteolytic cleavage of amyloid precursor protein (APP).
• APP builds up in the cell and turn in beta sheets.
• Amyloid fibrils form and stack up.

Question 20

What causes cystic fibrosis? [3 marks]

Answer 20

• Deletion of Phe at position 508 of the cystic fibrosis transmembrane conductance regulator (CTFR).
• Protein misfolds while it’s still in the ER.
• Protein gets degradation.

Question 21

What do prions rely on? [2 marks]

Answer 21

• Relies on minimisation of free energy

- A dynamic process brought about by the interaction of molecules resulting in a more stable aggregated structure.