Lecture 13 - Protein folding

Question 1

Protein structure

Answer 1

Highly specific for its desired effect

Question 2

What happens when the protein structure is not correct

Answer 2

The protein is considered mutated and can lead to misfolding

Question 3

Misfolding

Answer 3

Mislocalisation, ER accumulation, degradation, functional enzyme, tumour suppressor, and receptor loss (cystic fibrosis, hypercholesterolemia, phenylketonuria, cancer, α1-antitrypsin deficiency)

Extracellular toxic aggregates (amyloid plaques), intracellular deposits, neurodegenerative (Huntington’s, Parkinson’s, and Alzheimer’s etc)

Abnormal collagen assembly or extracellular matrix proteins. Connective tissue diseases

Question 4

Misfolding

Answer 4

Mislocalisation, ER accumulation, degradation, functional enzyme, tumour suppressor, and receptor loss (cystic fibrosis, hypercholesterolemia, phenylketonuria, cancer, α1-antitrypsin deficiency)

Extracellular toxic aggregates (amyloid plaques), intracellular deposits, neurodegenerative (Huntington’s, Parkinson’s, and Alzheimer’s etc)

Abnormal collagen assembly or extracellular matrix proteins. Connective tissue diseases (Scurvy, Marfan syndrome)

Abnormal cell or tissue morphology, impaired function (Cataracts, sickle cell anaemia)

Question 5

Exceptions to the highly specified rule

Answer 5

Intrinsically disordered proteins (IDP) - intentionally unfolded due to low complexity (not much amino acid variety - a low proportion of Val, Leu, Ile, Met, Phe, Trp, Tyr)

Question 6

Levinthal paradox

Answer 6

Folded to unfolded forms conversion: if it’s by random probability, then it would take an unacceptable and impossible amount of time before the correct conformation would be found

Question 7

Solutions to the Levinthal paradox

Answer 7

Intermediate states allow folding to occur

Question 8

Thermodynamics and spontaneity with Gibbs free energy

Answer 8

ΔG = ΔH - TΔS

• When ΔG is negative, a reaction is spontaneous
• Exothermic reactions (ΔH closer to 0), increases spontaneity - intermolecular forces increase spontaneity

Question 9

The hydrophobic effect

Answer 9

Hydrophobic and hydrophilic interactions with water increase the entropy which then causes an increase in spontaneity

Question 10

Chaperone proteins

Answer 10

Used to prevent misfolding and preventing aggregation due to non-specific interactions between different proteins