- Physical Review Journals
All JournalsPhysics Magazine
Access Provided by Xinjiang University

Physical Review E

Export citation

Export citation

Choose format for download:

Download Citation
  • Access by Xinjiang University

Elongation dynamics of amyloid fibrils: A rugged energy landscape picture

Chiu Fan Lee (李超帆)*

James Loken

Létitia Jean and David J. Vaux

  • Physics Department, Clarendon Laboratory, Oxford University, Oxford OX1 3PU, United Kingdom

  • Physics Department, Denys Wilkinson Building, Oxford University, Oxford OX1 3RH, United Kingdom

  • Sir William Dunn School of Pathology, Oxford University, Oxford OX1 3RE, United Kingdom

  • *Corresponding author. Present address: Max Planck Institute for the Physics of Complex Systems, Nothnitzer Str. 38, 01187 Dresden, Germany. E-mail: cflee@pks.mpg.de
PDF

Phys. Rev. E 80, 041906 – Published 6 October, 2009

DOI: https://doi.org/10.1103/PhysRevE.80.041906

Abstract

Protein amyloid fibrils are a form of linear protein aggregates that are implicated in many neurodegenerative diseases. Here, we study the dynamics of amyloid fibril elongation by performing Langevin dynamic simulations on a coarse-grained model of peptides. Our simulation results suggest that the elongation process is dominated by a series of local minimum due to frustration in monomer-fibril interactions. This rugged energy landscape picture indicates that the amount of recycling of monomers at the fibrils’ ends before being fibrilized is substantially reduced in comparison to the conventional two-step elongation model. This picture, along with other predictions discussed, can be tested with current experimental techniques.

View figure in article

Article Text

References (42)

  1. M. Sunde, L. C. Serpella, M. Bartlama, P. E. Frasera, M. B. Pepysa, and C. C. F. Blakea, J. Mol. Biol. 273, 729 (1997).
  2. C. M. Dobson, Nature (London) 426, 884 (2003).
  3. S. Radford, Trends Biochem. Sci. 25, 611 (2000).
  4. M. R. Sawaya et al., Nature (London) 447, 453 (2007).
  5. F. Chiti and C. M. Dobson, Nat. Chem. Biol. 5, 15 (2009).
  6. C. F. Lee, Phys. Rev. E 80, 031922 (2009).
  7. J. D. Harper and P. T. Lansbury, Annu. Rev. Biochem. 66, 385 (1997).
  8. D. Hall, N. Hirota, and C. Dobson, J. Mol. Biol. 351, 195 (2005).
  9. Y. Kusumoto, A. Lomakin, D. B. Teplow, and G. B. Benedek, Proc. Natl. Acad. Sci. U.S.A. 95, 12277 (1998).
  10. W. P. Esler, E. R. Stimson, J. M. Jennings, H. V. Vinters, J. R. Ghilardi, J. P. Lee, P. W. Mantyh, and J. E. Maggio, Biochemistry 39, 6288 (2000).
  11. F. Massi and J. E. Straub, Proteins 42, 217 (2001).
  12. T. Scheibel, J. Bloom, and S. L. Lindquist, Proc. Natl. Acad. Sci. U.S.A. 101, 2287 (2004).
  13. P. H. Nguyen, M. S. Li, G. Stock, J. E. Straub, and D. Thirumalai, Proc. Natl. Acad. Sci. U.S.A. 104, 111 (2007).
  14. S. R. Collins, A. Douglass, R. D. Vale, and J. S. Weissman, PLoS Biol. 2, e321 (2004).
  15. A. Lomakin, D. B. Teplow, D. A. Kirschner, and G. B. Benedek, Proc. Natl. Acad. Sci. U.S.A. 94, 7942 (1997).
  16. T. Ban, M. Hoshino, S. Takahashi, D. Hamada, K. Hasegawa, H. Naiki, and Y. Goto, J. Mol. Biol. 344, 757 (2004).
  17. T. P. J. Knowles et al., Proc. Natl. Acad. Sci. U.S.A. 104, 10016 (2007).
  18. K. Sneppen and G. Zocchi, Physics in Molecular Biology (Cambridge University Press, Cambridge, 2005).
  19. M. B. Jackson, Molecular and Cellular Biophysics (Cambridge University Press, Cambridge, 2006).
  20. This estimation comes from the property that the minimum of two variables drawn from two independent exponential distributions with rates λ1 and λ2 is again exponential distributed with rates λ1+λ2, and that the probability of having the minimum drawn from the first distribution is λ1/(λ1+λ2).
  21. C. Monthus and J.-P. Bouchaud, J. Phys. A 29, 3847 (1996).
  22. S. Peng, F. Ding, B. Urbanc, S. V. Buldyrev, L. Cruz, H. E. Stanley, and N. V. Dokholyan, Phys. Rev. E 69, 041908 (2004).
  23. H. D. Nguyen and C. K. Hall, Proc. Natl. Acad. Sci. U.S.A. 101, 16180 (2004).
  24. S. Santini, N. Mousseau, and P. Derreumaux, J. Am. Chem. Soc. 126, 11509 (2004).
  25. B. Urbanc, L. Cruz, S. Yun, S. V. Buldyrev, G. Bitan, D. B. Teplow, and H. E. Stanley, Proc. Natl. Acad. Sci. U.S.A. 101, 17345 (2004).
  26. G. Favrin, A. Irback, and S. Mohanty, Biophys. J. 87, 3657 (2004).
  27. R. Pellarin and A. Caflisch, J. Mol. Biol. 360, 882 (2006).
  28. N. Fawzi, Y. Okabe, E. Yap, and T. Headgordon, J. Mol. Biol. 365, 535 (2007).
  29. M. S. Li, D. K. Klimov, J. E. Straub, and D. Thirumalai, J. Chem. Phys. 129, 175101 (2008).
  30. Skjaeveland and K. Sneppen, Eur. Phys. J. E 2, 285 (2000).
  31. M. Daune, Molecular Biophysics: Structures in Motion (Oxford University Press, Oxford, 1999).
  32. J. Thijssen, Computational Physics, 2nd ed. (Cambridge University Press, Cambridge, 2007).
  33. R. Zwanzig, Proc. Natl. Acad. Sci. U.S.A. 85, 2029 (1988).
  34. Z. Farkas and T. Fülöp, J. Phys. A 34, 3191 (2001).
  35. A. T. Petkova, Y. Ishii, J. J. Balbach, O. N. Antzutkin, R. D. Leapman, F. Delaglio, and R. Tycko, Proc. Natl. Acad. Sci. U.S.A. 99, 16742 (2002).
  36. S. Yoon and W. J. Welsh, Protein Sci. 13, 2149 (2004).
  37. A. M. Fernandez-Escamilla, F. Rousseau, J. Schymkowitz, and L. Serrano, Nat. Biotechnol. 22, 1302 (2004).
  38. G. G. Tartaglia, A. Cavalli, R. Pellarin, and A. Caflisch, Protein Sci. 14, 2723 (2005).
  39. O. V. Galzitskaya, S. O. Garbuzynskiy, and M. Y. Lobanov, PLoS Comput. Biol. 2, e177 (2006).
  40. K. F. Dubay, A. P. Pawar, F. Chiti, J. Zurdo, C. M. Dobson, and M. Vendruscolo, J. Mol. Biol. 341, 1317 (2004).
  41. A. Pawar, K. Dubay, J. Zurdo, F. Chiti, M. Vendruscolo, and C. Dobson, J. Mol. Biol. 350, 379 (2005).
  42. Nereus, http://www-nereus.physics.ox.ac.uk/ (2008).

Outline

Information

Phys. Rev. E 80, 041906– Published 6 October, 2009
  • Received 25 December 2008

© 2009 American Physical Society

Sign In to Your Journals Account

Filter

Filter

Article Lookup

Enter a citation