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1. Introduction
2. What is a molecular chaperone?
3. Free energy landscape
4. The role of chaperones
5. How did it all start?
6. “Unfolding enzymes”
7. The discovery of Hsp60 (GroEL) and Hsp70 (DnaK)
8. The RubisCO binding protein
9. Overexpression of RubisCOL and RubisCOS
10. RubisCO assembly experiment
11. In vitro experiments
12. Chaperones can ‘proof-read’ the quality of protein folding
13. Evolutionary-inferred functional hierarchy of the chaperone network (I)
14. Evolutionary-inferred functional hierarchy of the chaperone network (II)
15. Evolutionary-inferred functional hierarchy of the chaperone network (III)
16. The structures of Hsp70 (and of DnaJ or Hsp40)
17. Hsp70s are abundant
18. Physiological and stress-related functions of Hsp70s
19. Cochaperones enable the protein to have many different functions
20. Hsp70 actively unfolds misfolded structures in aggregates
21. The disaggregation activity of Hsp70
22. The kinetic parameters and energy cost of Hsp70
23. ATP-fuelled Hsp70/DnaJ/NEF unfold inactive luciferase monomers
24. Unfolding consumes ATP
25. Unfolding consumes ATP, native refolding is spontaneous
26. The chaperone cycle of Hsp70 as an ATP-fuelled polypeptide unfoldase
27. 5 ATPs are required
28. What is the nature of the Hsp70 substrate: is it unfolded or misfolded?
29. Isolation of natively-unfolded and a stable oligomeric form of α-synuclein
30. Oligomeric α-synuclein inhibits Hsp70-mediated refolding
31. The fluorescence of the unique tryptophan in Hsp70 (DnaK) (I)
32. The fluorescence of the unique tryptophan in Hsp70 (DnaK) (II)
33. The fluorescence of the unique tryptophan in Hsp70 (DnaK) (III)
34. Model for substrate targeting
35. Entropic pulling and direct clamping
36. J-domain cochaperones
37. Evolution of J-domain cochaperones
38. Non-equilibrium temperatures
39. Model for the temperature-dependent conversion between Hsp70 states
40. 2020 single-molecule FRET approach
41. Hsp60 is also an ATP-consuming chaperone
42. ATP-dependent reversion of the misfolded state into the native state
43. Urea-treated MDH at 37°C
44. The presence of GroELS and ATP repopulates native species
45. Summary
46. “Sine Sole Sileo”
47. Acknowledgments

Topics Covered

• Hsp70s are conserved molecular chaperones
• They can prevent protein aggregation, they actively unfold and solubilize aggregates and pull translocating proteins across membranes
• A unifying mechanism has been proposed whereby Hsp70 uses the energy of ATP hydrolysis to recruit a force of entropic origin to locally unfold aggregates or pull proteins across membranes
• Entropic pulling is a simple mechanism, reconciling earlier conflicting data
• This provides a framework for curing therapies of protein misfolding diseases
• Alzheimer's disease and aging

Links

Series:

• Molecular Chaperones

Categories:

• Biochemistry
• Cell Biology

External Links

• On the evolution of chaperones and co-chaperones and the exponential expansion of proteome complexity
• Bacterial Hsp90 mediates the degradation of aggregation-prone Hsp70-Hsp40 substrates preferentially by HslUV proteolysis

Talk Citation

Goloubinoff, P. (2007, October 1). Towards a unifying mechanism for the Hsp70 chaperones [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved April 17, 2025, from https://doi.org/10.69645/PFZR9897.
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Publication History

• Published on October 1, 2007
• Archived on February 25, 2021

Financial Disclosures

• Prof. Pierre Goloubinoff has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.