Lec13 - Protein Folding

Question 1

Name 4 types of disease associated with protein misfolding (and prominent examples of each)

Answer 1

1. Mislocalisation (e.g., Hypercholesterolaemia, CF)
2. Accumulation of Toxic Aggregates (e.g., amyloid plaques outside cell; intracellular deposits can be neurodegenerative -> Huntington’s, Alzheimer’s etc.)
3. Abnormal collagen assembly or extracellular matrix proteins (e.g., scurvy)
4. Abnormal cell or tissue morphology (e.g., sickle cell anaemia, cataracts)

Question 2

What is the common structural feature of Intrinsically Disordered Proteins (IDPs)?

Answer 2

Compositional bias (few AAs over-represented, lack of hydrophobic AAs)

Question 3

How do IDPs function without folding like normal proteins do?

Answer 3

Some fold UPON BINDING to their biological targets; some may have flexible linker proteins to facilitate assembly formation

Question 4

What is the most popular solution to the Levinthal paradox?

Answer 4

Rather than random conformational search, proteins fold through intermediate states (a pathway)

Question 5

What two things can drive a spontaneous reaction (ΔG < 0)?

Answer 5

A decrease in enthalpy (ΔH < 0) or an increase in entropy (ΔS > 0)

Question 6

What aspects of protein folding can cause ΔH to be negative (favourable)?

Answer 6

Formation of H bonds, electostatic interactions, van der Waals
Folding brings groups close together and generates opportunities for favourable interactions

Question 7

What causes protein folding to be entropically favourable despite folding restricting degrees of freedom?

Answer 7

HYDROPHOBIC EFFECT: water molecules increase in their randomness; hydrophobic side chains associate with each other causing a chain to collaps into a hydrophobic core

Question 8

Which enzyme was used in experiments to determine whether proteins can fold unassisted?

Answer 8

Ribonuclease

Question 9

Can proteins fold unassisted?

Answer 9

Technically yes, all the information required for a protein to fold correctly is contained within the primary Amino Acid sequence

Question 10

Why is protein folding more complicated in the cell environment?

Answer 10

Proteins are not free flowing in the cytoplasm (crowded environment with potential for non-specific interactions)
Chaperones required to stabilise intermediates