Summary
Molecular chaperones ensure proteins achieve their functional 3D conformations without aggregating. Key systems include Hsp70, Chaperonins (GroEL-GroES), and Hsp90, operating via ATP-dependent cycles that rescue misfolded intermediates.
Key Points
- 1Hsp70 binds hydrophobic regions to prevent aggregation
- 2Chaperonins provide isolated folding chambers
- 3ATP hydrolysis powers conformational cycles
- 4Chaperone failure linked to neurodegenerative diseases
While the amino acid sequence contains all the information needed for folding (Anfinsen's dogma), the crowded cellular environment necessitates molecular chaperones to ensure proper protein folding.
Why Chaperones Are Necessary
The cellular environment presents challenges not found in test tube refolding experiments:
- Macromolecular crowding: Protein concentrations of 300-400 mg/mL
- Nascent chain vulnerability: Incomplete proteins cannot fold properly
- Aggregation risk: Exposed hydrophobic surfaces promote intermolecular interactions
Major Chaperone Systems
Hsp70 (DnaK in bacteria)
The Hsp70 system is the most versatile chaperone:
- Binds short hydrophobic peptide segments on nascent or misfolded proteins
Chaperonins (GroEL-GroES / TRiC)
Chaperonins provide a protected folding environment:
- GroEL: Double-ring structure forming a central cavity
- GroES: Lid that caps the folding chamber
- Creates a hydrophilic isolation chamber where proteins can fold in isolation
Hsp90
Hsp90 specializes in signaling proteins:
How Chaperones Work
Chaperones don't provide folding instructions. Instead, they:
1. Shield hydrophobic surfaces from aggregation
2. Provide isolated folding environments (chaperonins)
3. Unfold kinetically trapped intermediates using ATP
4. Smooth the energy landscape toward productive folding
Chaperones and Disease
Failure of chaperone systems is implicated in proteopathies: