Chapter 4.4: Protein Denaturation and Folding

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Chapter 4.4 Protein Denaturation and Folding

• CHEM 7784
• Biochemistry
• Professor Bensley

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CHAPTER 4.4 Proteins Denaturation and Folding
Todays Objectives - To learn and understand

• Protein folding and denaturation

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Protein Stability and Folding

• A proteins function depends on its
  three- dimensional structure.
• Loss of structural integrity with accompanying
  loss of activity is called denaturation
• Proteins can be denatured by
• heat or cold
• pH extremes
• organic solvents
• chaotropic agents urea and guanidinium
  hydrochloride

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Ribonuclease Refolding Experiment
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How Can Proteins Fold So Fast?

• Ribonuclease A (RNase A) will refold to native
  structure spontaneously (1 minute)
• gt1050 possible conformations
• If 10-13 sec per conformation would take 1030
  years to sample enough to determine structure
• Search for the minimum is not random because the
  direction toward the native structure is
  thermodynamically most favorable

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Factors Driving Protein Folding
DG DH - TDS

• Conformational entropy AB ? C decreases entropy
  (unfavorable)
• Non-covalent interactions give favorable enthalpy
  value
• Hydrophobic effect increases entropy by freeing
  water (favorable)

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Chaperones Prevent Misfolding
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Chaperonins
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Chapter 4 Summary
In this chapter, we learned about

• The two most important secondary structures
• ? helixes
• ? sheets
• How properties and function of fibrous proteins
  are related
• How to determine three-dimensional structures of
  proteins
• One of the largest unsolved puzzles in modern
  biochemistry How do proteins fold?