• Introduction to Protein Folding and Misfolding
• 69 min
  1. Protein folding and misfolding: from theory to therapy

  • Prof. Christopher Dobson
• Stability and Kinetics of Protein Folding
• 55 min
  2. Mechanisms of protein folding reactions

  • Prof. Thomas Kiefhaber
• Protein Folding Theory
• 53 min
  3. Mapping disordered proteins with single-molecule FRET

  • Dr. Hagen Hofmann
• Protein Folding Simulations
• 36 min
  4. Protein folding

  • Prof. Eugene Shakhnovich
• 42 min
  5. Simulating protein folding with full atomistic detail

  • Prof. Vijay Pande
• 58 min
  6. Molecular dynamics simulations of protein dynamics, unfolding and misfolding

  • Prof. Valerie Daggett
• Protein Folding Inside the Cell: Chaperones
• 42 min
  7. Protein folding Inside the cell: macromolecular crowding and protein aggregation

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

  • Prof. Dr. F. Ulrich Hartl
• 60 min
  9. Quality control of proteins mislocalized to the cytosol

  • Dr. Ramanujan Hegde
• Protein Misfolding and Disease
• 44 min
  10. Protein aggregation, metals and oxidative stress in neurodegenerative diseases

  • Prof. David Allsop
• Protein Design
• 33 min
  11. Designing proteins with life sustaining activities 1

  • Prof. Michael Hecht
• 24 min
  12. Designing proteins with life sustaining activities 2

  • Prof. Michael Hecht
• 48 min
  13. Folding and design of helical repeat proteins

  • Prof. Lynne Regan
• 44 min
  14. Design and engineering of zinc-finger domains

  • Prof. Jacqui Matthews
• 47 min
  15. Prediction and design of protein structures and interactions

  • Prof. David Baker
• Amyloid Fibrils: Structure, Formation and Nanotechnology
• 39 min
  16. Amyloid fibrils as functional nanomaterials

  • Prof. Juliet Gerrard
• 37 min
  17. Functional amyloid fibrils from fungi and viruses

  • Prof. Margaret Sunde
• Intrinsically disordered Proteins
• 40 min
  18. Fuzzy protein theory for disordered proteins

  • Prof. Monika Fuxreiter
• Intersection of RNA, translation and protein aggregation.
• 47 min
  19. Expanding roles of RNA-binding proteins in neurodegenerative diseases

  • Prof. Aaron D. Gitler
• Proteostasis
• 49 min
  20. Adapting proteostasis to ameliorate aggregation-associated amyloid diseases

  • Dr. Jeffery W. Kelly
• Archived Lectures *These may not cover the latest advances in the field
• 60 min
  21. Amyloidosis: disease caused by amyloid

  • Prof. Mark Pepys
• 34 min
  22. Protein folding and dynamics from single molecule spectroscopy

  • Prof. Dr. Benjamin Schuler
• 41 min
  23. Prion diseases

  • Prof. Fred Cohen
• 31 min
  24. Basic studies of protein folding and stability: the folding of related protein families

  • Dr. Jane Clarke
• 38 min
  25. Titin I27: a protein with a complex folding landscape

  • Dr. Jane Clarke
• 49 min
  26. Novel proteins from designed combinatorial libraries

  • Prof. Michael Hecht
• 47 min
  27. Fast folding dynamics of small proteins: placing limits on diffusional limits

  • Dr. Stephen Hagen
• 35 min
  28. The sequence determinants of amyloid fibril formation

  • Prof. Fabrizio Chiti

Printable Handouts

PDF

Navigable Slide Index

1. Introduction
2. Titin I27 - general description
3. Folding - unfolding plot for Titin I27
4. Environmental conditions change folding pathway
5. TI27 mutants - unfolding pathways
6. Parallel folding pathways
7. How can we analyze these data?
8. High and low-stress unfolding pathway
9. Temperature can change the unfolding pathway
10. Mutations can change the folding pathway
11. Titin - a protein experiencing mechanical stress
12. Titin - effects of force
13. How does Titin resist unfolding under stress?
14. Addition of force lowers the unfolding energy barrier
15. Using AFM to investigate protein unfolding
16. First experiments - using whole proteins
17. The ideal protein - 8 repeats of I27
18. The protein - 8 repeats of I27 - unfolding
19. AFM experiments let comparison with simulations
20. Simulations - first step - forming an intermediate
21. Humps appear on the plot of unfolding
22. Mutation in the A-strand does not affect unfolding
23. A-strand lacking intermediate is stable
24. TI I27 has an intermediate on the unfolding pathway
25. Protein engineering for analysis of unfolding
26. Rationale
27. Different mutanst affect the folding force differently
28. Titin forced unfolding pathway
29. TS under force vs. physiological conditions
30. What can alter the protein unfolding landscape
31. Single molecular experiments let us see rare events
32. How do multi-domain proteins avoid aggregation
33. Tandem proteins aggregate faster
34. Strategies of aggregation avoidance
35. Titin domains behave independently
36. Strategy 2 - weak modules next to strong modules
37. Strategy 3 - select for certain residues
38. Removing the prolines speeds up aggregation
39. Strategy 4 - diversify the sequence of domains (1)
40. Strategy 4 - diversify the sequence of domains (2)
41. Evolutionary pressure to diversify sequences
42. How similar are Titin domains?
43. Conclusion
44. Acknowledgments

Topics Covered

• Examination of the folding of titin 127
• Evolution of the protein to withstand stress from mutation, the environment and to withstand mechanical force in the muscle
• Use of a combination of protein engineering, kinetic and thermodynamic measurements, computer simulations and single molecule atomic force microscopy to understand how evolution acts on protein sequences to allow them to adapt to stressful conditions, probably explaining why immunoglobulin-like proteins are used so successfully in evolution to perform a number of functions

Links

Series:

• Protein Folding, Aggregation and Design

Categories:

• Biochemistry

Talk Citation

Publication History

• Published on October 1, 2007
• Archived on April 17, 2016

Financial Disclosures

• Dr. Jane Clarke has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.