Protein Synthesis: Protein Folding and Molecular Chaperones

Overview

• Focus on protein folding in Chapter 22.
• Relationship between protein folding and molecular chaperones.
• Chaperones use ATP hydrolysis to assist in protein refolding.
• Discuss three types of molecular chaperones:
  • Trigger Factor
  • DNA K
  • GroEL-GroES Complex

Trigger Factor

• Location & Function:
  • Positioned just outside the ribosome's exit tunnel.
  • First molecular chaperone encountered by most proteins.
  • Binds to nascent polypeptide as it exits the ribosome.
• Mechanism:
  • Binds to hydrophobic patches on the protein which are usually internal.
  • May release polypeptides to allow for independent folding or pass them to another chaperone.
• Visualization:
  • Trigger Factor is highlighted in red, green, blue, and yellow.
  • Nascent polypeptide highlighted in magenta.

DNA K

• Characteristics:
  • Not associated with the ribosome.
  • Clamps down on proteins and then releases them.
• Function & Mechanism:
  • Binds to exposed hydrophobic patches indicating misfolding.
  • Allows proteins to refold by releasing them.
• Visualization:
  • DNA K is highlighted in green; the target protein in yellow.

GroEL-GroES Complex

• Structure:
  • Complex of two heptameric (seven-membered) rings.
  • Each ring binds seven ATP molecules.
• Function:
  • Provides a protected environment for protein folding inside each ring.
  • Recognizes exposed hydrophobic patches on misfolded proteins.
• Mechanism:
  • Binding of GroES cap releases the peptide into the GroEL barrel.
  • ATP hydrolysis subsequently releases the peptide within the chamber, allowing it to refold.
• Visualization:
  • Two rings are centrally positioned back to back in the complex.

Conclusion

• Molecular chaperones aid in protein folding by providing a suitable environment, not by folding the proteins themselves.

Next Lesson

• Exploration of potential post-translational modifications to proteins.