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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

Clarke, J. (2007, October 1). Titin I27: a protein with a complex folding landscape [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 22, 2024, from https://doi.org/10.69645/SBBU9900.
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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.