Lecture 5: Protein Folding I

Question 1

LO1: Describe the determinants of protein folding

Answer 1

1. Secondary structure (for an efficient packing)
2. Hierarchical folding
3. Hydrophobic effect
4. Context dependent

Question 2

LO2: Describe protein secondary structure

Answer 2

Alpha helixes and beta sheets for stability

Question 3

LO3: Understand the concept of molten globule

Answer 3

EVENTS:

1. Rapid formation of secondary structure
2. Formation of domains thru cooperative aggregation (concept of folding nuclei)
3. Formation of assembled domains (concept of molten globule)***
4. Adjustment of conformation
5. More rigid structure

Question 4

Secondary structures

Answer 4

Alpha helixes and Beta sheets for stability

Question 5

Alpha helix

Answer 5

Stabilized by H bonds b2n NH and C=O groups; H bonds form 4 aa resides

Question 6

Beta sheets

Answer 6

Composed of 2 or more polypeptide chains: B-strands

Question 7

Superhelix (alpha helix coiled coil)

Answer 7

Serves as structural role, long protein fibers, 2 helices in a-keratin with each other by weak interactions (Van der Waals forces and ionic interactions)

**Characterized by central region of 300 AA that contains HEPTAD REPEATS (7 AA) @ middle

Question 8

At lower energy

Answer 8

Molecules are more stable (inverse relationship)

Question 9

Molten Globule State

Answer 9

An intermediate conformational state b2n NATIVE and fully unfolded/denatured states of globular protein;

Also a compact globule with a “molten” side-chain structure that is primarily STABILIZED BY NONSPECIFIC INTERACTIONS

Question 10

Molten Globule State Characteristics

Answer 10

1. Presence of native-like content of sec structure
2. Absence of a specific tertiary structure produced by tight packing of AA side chains
3. Compactness in overall shape of protein molecule with a radius of 10 to 30% larger than that of the naive state
4. The presence of a loosely packed hydrophobic core that increases the hydrophobic SA accessible to solvent
5. It is not specific and occurs in early stage of protein folding

Question 11

Summary

Answer 11

• Protein folding stability governed by noncov interactions and hydrophobic interactions
• Protein folding (PF)= cooperative process
• PF obeys to thermodynamics’ law and prefers low E state
• Molten globule state is b2n native and full unfolded/denatured state of globular protein