No data available.
Please log in to see this content.
You have no subscription access to this content.
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.
The full text of this article is not currently available.
Kinetics of fragmentation and dissociation of two-strand protein filaments: Coarse-grained simulations and experiments
F. Oosawa and S. Asakura, Thermodynamics of the Polymerization of Protein (Academic Press, Waltham MA, 1975).
B. Alberts, Molecular Biology of the Cell (Taylor & Francis, New York, 2002).
H. J. Kinosian, L. A. Selden, J. E. Estes, and L. C. Gershman, “Actin filament annealing in the presence of ATP and phalloidin,” Biochemistry 32, 12353–12357 (1993).
D. Vavylonis, Q. Yang, and B. O’Shaughnessy, “Actin polymerization kinetics, cap structure, and fluctuations,” Proc. Natl. Acad. Sci. U. S. A. 102, 8543–8548 (2005).
E. Andrianantoandro, L. Blanchoin, D. Sept, J. A. McCammon, and T. D. Pollard, “Kinetic mechanism of end-to-end annealing of actin filaments,” J. Mol. Biol. 312, 721–730 (2001).
I. Fujiwara, S. Takahashi, H. Tadakuma, T. Funatsu, and S. Ishiwata, “Microscopic analysis of polymerization dynamics with individual actin filaments,” Nat. Cell Biol. 4, 666–673 (2002).
J. R. Kuhn and T. D. Pollard, “Real-time measurements of actin filament polymerization by total internal reflection fluorescence microscopy,” Biophys. J. 88, 1387–1402 (2005).
J. Fass, C. Pak, J. Bamburg, and A. Mogilner, “Stochastic simulation of actin dynamics reveals the role of annealing and fragmentation,” J. Theor. Biol. 252, 173–183 (2008).
T. P. J. Knowles, C. A. Waudby, G. L. Devlin, S. I. A. Cohen, A. Aguzzi, M. Vendruscolo, E. M. Terentjev, M. E. Welland, and C. M. Dobson, “An analytical solution to the kinetics of breakable filament assembly,” Science 326, 1533–1537 (2009).
J. Adamcik, J.-M. Jung, J. Flakowski, P. De Los Rios, G. Dietler, and R. Mezzenga, “Understanding amyloid aggregation by statistical analysis of atomic force microscopy images,” Nat. Nanotechnol. 5, 423–428 (2010).
J. Käs, H. Strey, J. X. Tang, D. Finger, R. Ezzell, E. Sackmann, and P. A. Janmey, “F-actin, a model polymer for semiflexible chains in dilute, semi-dilute, and liquid crystalline solutions,” Biophys. J. 70, 609–625 (1996).
M. Groenning, R. I. Campos, D. Hirschberg, P. Hammarstrom, and B. Vestergaard, “Considerably unfolded transthyretin monomers preceed and exchange with dynamically structured amyloid protofibrils,” Sci. Rep. 5, 11443 (2015).
F. Gittes, B. Mickey, J. Nettleton, and J. Howard, “Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape,” J. Cell Biol. 120, 923–934 (1993).
T. P. J. Knowles, A. W. Fitzpatrick, S. Meehan, H. R. Mott, M. Vendruscolo, C. M. Dobson, and M. E. Welland, “Role of intermolecular forces in defining material properties of protein nanofibrils,” Science 318, 1900–1903 (2007).
J. F. Smith, T. P. J. Knowles, C. M. Dobson, C. E. Macphee, and M. E. Welland, “Characterization of the nanoscale properties of individual amyloid fibrils,” Proc. Natl. Acad. Sci. U. S. A. 103, 15806–15811 (2006).
W. Han and K. Schulten, “Fibril Elongation by Aβ17-42: Kinetic network analysis of hybrid-resolution molecular dynamics simulations,” J. Am. Chem. Soc. 136, 12450 (2014).
A. Zaccone, I. Terentjev, L. DiMichele, and E. M. Terentjev, “Fragmentation and depolymerisation of non-covalently bonded filaments,” J. Chem. Phys. 142, 114905 (2015).
J. L. Jiménez, E. J. Nettleton, M. Bouchard, C. V. Robinson, C. M. Dobson, and H. R. Saibil, “The protofilament structure of insulin amyloid fibrils,” Proc. Natl. Acad. Sci. U. S. A. 99, 9196–9201 (2002).
A. K. Buell, J. R. Blundell, C. M. Dobson, M. E. Welland, E. M. Terentjev, and T. P. J. Knowles, “Frequency factors in a landscape model of filamentous protein aggregation,” Phys. Rev. Lett. 104, 228101 (2010).
J. W. Chu and G. A. Voth, “Allostery of actin filaments: Molecular dynamics simulations and coarse-grained analysis,” Proc. Natl. Acad. Sci. U. S. A. 102, 13111–13116 (2005).
M. G. Saunders and G. A. Voth, “Water molecules in the nucleotide binding cleft of actin: Effects on subunit conformation and implications for ATP hydrolysis,” J. Mol. Biol. 413, 279 (2011).
T. Fujii, A. H. Iwane, T. Yanagida, and K. Namba, “Direct visualization of secondary structures of F-actin by electron cryomicroscopy,” Nature 467, 724 (2010).
M. Matsumoto and T. Nishimura, “Mersenne twister: A 623-dimensionally equidistributed uniform pseudo-random number generator,” ACM Trans. Model. Comput. Simul. 8, 3–30 (1998).
Article metrics loading...
While a significant body of investigations have been focused on the process of protein self-assembly, much less is understood about the reverse process of a filament breaking due to thermal motion into smaller fragments, or depolymerization of subunits from the filament ends. Indirect evidence for actin and amyloid filament fragmentation has been reported, although the phenomenon has never been directly observed either experimentally or in simulations. Here we report the direct observation of filament depolymerization and breakup in a minimal, calibrated model of coarse-grained molecular simulation. We quantify the orders of magnitude by which the depolymerization rate from the filament ends k
off is larger than fragmentation rate k
− and establish the law k
− = exp[(ε‖ − ε⊥)/k
T] = exp[0.5ε/k
T], which accounts for the topology and energy of bonds holding the filament together. This mechanism and the order-of-magnitude predictions are well supported by direct experimental measurements of depolymerization of insulin amyloid filaments.
Full text loading...
Most read this month