Lec 8: Tertiary Structure, Protein Folding, Quaternary Structure

Tertiary Structure

DEFINITION: The complete three-dimensional arrangement of all atoms in a single polypeptide chain

5 Key Features of tertiary structure

1. HELICES AND SHEETS PACK TOGETHER CLOSELY

• Minimize empty space

• Maximize van der Waals contacts

2. CONNECTING SEGMENTS ARE SHORT AND DIRECT

• Loops and turns connect secondary structures

• Minimize chain length between elements

3. PROTEINS FOLD TO MAXIMIZE STABILITY

• Driven by thermodynamics

• Native state is the energy minimum

4. HYDROPHOBIC RESIDUES BURIED IN CORE

• Nonpolar side chains cluster inside

• Drives the hydrophobic effect

5. HYDROPHILIC RESIDUES ON SURFACE

• Polar and charged groups face solvent

• Enable solubility and interactions

The Thermodynamics of Protein Folding

• describe: unfolded state, folded state, folding funnel and Net ΔG (what does it allow)

• high or low entropy, shape?

UNFOLDED STATE:

• High entropy (many conformations); High energy; Exposed hydrophobic residues

FOLDED STATE:

• Low entropy (single conformation); Lower energy; Buried hydrophobic residues

THE FOLDING FUNNEL:

• Wide at top: many unfolded conformations

• Narrow at bottom: single native state

• Proteins "roll downhill" to native state

NET ΔG: -20 to -40 kJ/mol -> Small but significant; Allows flexibility and regulation

hi