Role of filament annealing in the kinetics and thermodynamics of nucleated polymerization

Michaels, Thomas C. T.; Knowles, Tuomas P. J.,

doi:10.1063/1.4880121

Title: Role of filament annealing in the kinetics and thermodynamics of nucleated polymerization

Full Record
Other Related Research

Abstract

The formation of nanoscale protein filaments from soluble precursor molecules through nucleated polymerization is a common form of supra-molecular assembly phenomenon. This process underlies the generation of a range of both functional and pathological structures in nature. Filament breakage has emerged as a key process controlling the kinetics of the growth reaction since it increases the number of filament ends in the system that can act as growth sites. In order to ensure microscopic reversibility, however, the inverse process of fragmentation, end-to-end annealing of filaments, is a necessary component of a consistent description of such systems. Here, we combine Smoluchowski kinetics with nucleated polymerization models to generate a master equation description of protein fibrillization, where filamentous structures can undergo end-to-end association, in addition to elongation, fragmentation, and nucleation processes. We obtain self-consistent closed-form expressions for the growth kinetics and discuss the key physics that emerges from considering filament fusion relative to current fragmentation only models. Furthermore, we study the key time scales that describe relaxation to equilibrium.

Authors:

Michaels, Thomas C. T.; Knowles, Tuomas P. J., ^[1]

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW (United Kingdom)

Publication Date:: Sat Jun 07 00:00:00 EDT 2014

OSTI Identifier:: 22304271

Resource Type:: Journal Article

Journal Name:: Journal of Chemical Physics

Additional Journal Information:: Journal Volume: 140; Journal Issue: 21; Other Information: (c) 2014 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0021-9606

Country of Publication:: United States

Language:: English

Subject:: 37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; 77 NANOSCIENCE AND NANOTECHNOLOGY; ANNEALING; KINETICS; MOLECULES; NANOSTRUCTURES; NUCLEATION; POLYMERIZATION; PROTEINS; THERMODYNAMICS

Citation Formats


                    Michaels, Thomas C. T., and Knowles, Tuomas P. J.,. Role of filament annealing in the kinetics and thermodynamics of nucleated polymerization.  United States: N. p., 2014. 
        Web.  doi:10.1063/1.4880121.

Copy to clipboard


                    Michaels, Thomas C. T., & Knowles, Tuomas P. J.,. Role of filament annealing in the kinetics and thermodynamics of nucleated polymerization.  United States.  https://doi.org/10.1063/1.4880121

Copy to clipboard


                    Michaels, Thomas C. T., and Knowles, Tuomas P. J.,. 2014.  
        "Role of filament annealing in the kinetics and thermodynamics of nucleated polymerization".  United States.  https://doi.org/10.1063/1.4880121.

Copy to clipboard


                    
@article{osti_22304271,

  title        = {Role of filament annealing in the kinetics and thermodynamics of nucleated polymerization},

  author       = {Michaels, Thomas C. T. and Knowles, Tuomas P. J.,},

  abstractNote = {The formation of nanoscale protein filaments from soluble precursor molecules through nucleated polymerization is a common form of supra-molecular assembly phenomenon. This process underlies the generation of a range of both functional and pathological structures in nature. Filament breakage has emerged as a key process controlling the kinetics of the growth reaction since it increases the number of filament ends in the system that can act as growth sites. In order to ensure microscopic reversibility, however, the inverse process of fragmentation, end-to-end annealing of filaments, is a necessary component of a consistent description of such systems. Here, we combine Smoluchowski kinetics with nucleated polymerization models to generate a master equation description of protein fibrillization, where filamentous structures can undergo end-to-end association, in addition to elongation, fragmentation, and nucleation processes. We obtain self-consistent closed-form expressions for the growth kinetics and discuss the key physics that emerges from considering filament fusion relative to current fragmentation only models. Furthermore, we study the key time scales that describe relaxation to equilibrium.},

  doi          = {10.1063/1.4880121},

  url          = {https://www.osti.gov/biblio/22304271},
  journal      = {Journal of Chemical Physics},

  issn         = {0021-9606},

  number       = 21,

  volume       = 140,

  place        = {United States},

  year         = {Sat Jun 07 00:00:00 EDT 2014},

  month        = {Sat Jun 07 00:00:00 EDT 2014}

}

Copy to clipboard

Journal Article:

https://doi.org/10.1063/1.4880121

Other availability

Find in Google Scholar

Search WorldCat to find libraries that may hold this journal

Save / Share:

Export Metadata

Save to My Library

Similar records in OSTI.GOV collections:

Dynamics of protein aggregation and oligomer formation governed by secondary nucleation

Journal Article Michaels, Thomas; Lazell, Hamish; Arosio, Paolo; ... - Journal of Chemical Physics

The formation of aggregates in many protein systems can be significantly accelerated by secondary nucleation, a process where existing assemblies catalyse the nucleation of new species. In particular, secondary nucleation has emerged as a central process controlling the proliferation of many filamentous protein structures, including molecular species related to diseases such as sickle cell anemia and a range of neurodegenerative conditions. Increasing evidence suggests that the physical size of protein filaments plays a key role in determining their potential for deleterious interactions with living cells, with smaller aggregates of misfolded proteins, oligomers, being particularly toxic. It is thus crucial tomore »« less
https://doi.org/10.1063/1.4927655
From Aβ Filament to Fibril: Molecular Mechanism of Surface-Activated Secondary Nucleation from All-Atom MD Simulations

Journal Article Schwierz, Nadine; Frost, Christina; Geissler, Phillip; ... - Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry

Secondary nucleation pathways in which existing amyloid fibrils catalyze the formation of new aggregates and neurotoxic oligomers are of immediate importance for the onset and progression of Alzheimer’s disease. Here, we apply extensive all-atom molecular dynamics simulations in explicit water to study surface-activated secondary nucleation pathways at the extended lateral β-sheet surface of a preformed Aβ9–40 filament. Calculation of free-energy profiles allows us to determine binding free energies and conformational intermediates for nucleation complexes consisting of 1–4 Aβ peptides. In addition, we combine the free-energy profiles with position-dependent diffusion profiles to extract complementary kinetic information and macroscopic growth rates. Singlemore »« less
https://doi.org/10.1021/acs.jpcb.6b10189
Insights into the variability of nucleated amyloid polymerization by a minimalistic model of stochastic protein assembly

Journal Article Eugène, Sarah; Doumic, Marie; Xue, Wei-Feng; ... - Journal of Chemical Physics

Self-assembly of proteins into amyloid aggregates is an important biological phenomenon associated with human diseases such as Alzheimer’s disease. Amyloid fibrils also have potential applications in nano-engineering of biomaterials. The kinetics of amyloid assembly show an exponential growth phase preceded by a lag phase, variable in duration as seen in bulk experiments and experiments that mimic the small volumes of cells. Here, to investigate the origins and the properties of the observed variability in the lag phase of amyloid assembly currently not accounted for by deterministic nucleation dependent mechanisms, we formulate a new stochastic minimal model that is capable ofmore »« less
https://doi.org/10.1063/1.4947472
Structure of a Longitudinal Actin Dimer Assembled by Tandem W Domains: Implications for Actin Filament Nucleation

Journal Article Rebowski, Grzegorz; Namgoong, Suk; Boczkowska, Malgorzata; ... - J. Mol. Biol.

Actin filament nucleators initiate polymerization in cells in a regulated manner. A common architecture among these molecules consists of tandem WASP homology 2 domains (W domains) that recruit three to four actin subunits to form a polymerization nucleus. We describe a low-resolution crystal structure of an actin dimer assembled by tandem W domains, where the first W domain is cross-linked to Cys374 of the actin subunit bound to it, whereas the last W domain is followed by the C-terminal pointed end-capping helix of thymosin {beta}4. While the arrangement of actin subunits in the dimer resembles that of a long-pitch helixmore »« less
https://doi.org/10.1016/j.jmb.2010.08.040
WH2 and proline-rich domains of WASP-family proteins collaborate to accelerate actin filament elongation

Journal Article Bieling, Peter; Hansen, Scott; Akin, Orkun; ... - EMBO Journal

WASP-family proteins are known to promote assembly of branched actin networks by stimulating the filament-nucleating activity of the Arp2/3 complex. Here, we show that WASP-family proteins also function as polymerases that accelerate elongation of uncapped actin filaments. When clustered on a surface, WASP-family proteins can drive branched actin networks to grow much faster than they could by direct incorporation of soluble monomers. This polymerase activity arises from the coordinated action of two regulatory sequences: (i) a WASP homology 2 (WH2) domain that binds actin, and (ii) a proline-rich sequence that binds profilin–actin complexes. In the absence of profilin, WH2 domainsmore »« less
https://doi.org/10.15252/embj.201797039

Full Text Available

Similar Records