• Overview of Molecular Chaperones
• 34 min
  1. History of the molecular chaperone concept: roles in assembly processes

  • Prof. Emeritus R. John Ellis
• 34 min
  2. Chaperone mechanisms in cellular protein folding

  • Prof. Dr. F. Ulrich Hartl
• Prokaryotic Molecular Chaperones
• 38 min
  3. Mechanistic aspects of chaperonin GroEL/ES function

  • Prof. Amnon Horovitz
• 99 min
  4. Structure and function of the ATP-dependent Clp chaperone/protease machines

  • Dr. Michael R. Maurizi
• 32 min
  5. The role of chaperones and Sec machinery in protein secretion

  • Prof. Koreaki Ito
• 44 min
  6. How can molecular chaperones repair damaged protein structures?

  • Prof. Pierre Goloubinoff
• 32 min
  7. Disulfide bond formation in vivo

  • Prof. James Bardwell
• Eukaryotic Molecular Chaperones
• 39 min
  8. Overview of eukaryotic molecular chaperones in the cytosol

  • Dr. Jason C. Young
• 36 min
  9. Chaperonin-containing TCP-1 (CCT), actin springs, and protein folding fluxes

  • Prof. Keith Willison
• 35 min
  10. The functions of the Hsp70 system

  • Prof. Jeffrey L. Brodsky
• 26 min
  11. Hsp90: a chaperone for protein kinases and hormone receptors

  • Dr. David Toft
• Role of Chaperones in Diseases
• 38 min
  12. The roles of molecular chaperones in bacterial infection

  • Prof. Tomoko Yamamoto
• 46 min
  13. Role of chaperonin-like proteins in Bardet-Biedl syndrome

  • Dr. Michel R. Leroux
• 53 min
  14. Roles for molecular chaperones in cystic fibrosis

  • Prof. Douglas M. Cyr
• 51 min
  15. Targeting cancer: designing drugs against Hsp90

  • Dr. Gabriela Chiosis
• Archived Lectures *These may not cover the latest advances in the field
• 29 min
  16. Overview of prokaryotic molecular chaperones

  • Prof. Walid A. Houry
• 47 min
  17. The biogenesis of E. coli inner membrane proteins

  • Dr. Joen Luirink
• 39 min
  18. Mechanism of chaperone action of small heat shock proteins

  • Prof. Elizabeth Vierling
• 22 min
  19. ClpB: a chaperone for protein disaggregation

  • Prof. Michal Zolkiewski
• 38 min
  20. The roles of chaperonins in bacteria

  • Dr. Peter Lund
• 44 min
  21. Towards a unifying mechanism for the Hsp70 chaperones

  • Prof. Pierre Goloubinoff
• 29 min
  22. Adaptor mediated activation of the Hsp100/ Clp protein ClpC controls general and regulatory proteolysis in Bacillus subtilis

  • Prof. Dr. Kursad Turgay
• 33 min
  23. Hsp31: a general stress protein of Escherichia coli

  • Prof. Francois Baneyx
• 46 min
  24. Hsp104: a specialized chaperone for protein disaggregation

  • Dr. John R. Glover
• 47 min
  25. Molecular chaperones and handling of abnormal proteins in neurodegenerative disorders

  • Prof. Michael Sherman
• 20 min
  26. The role of chaperones in Parkinson's disease

  • Dr. Konstanze F. Winklhofer

Printable Handouts

PDF

Navigable Slide Index

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

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.