Actin Filament Strain Promotes Severing and Cofilin Dissociation

Anthony C. Schramm, Glen M. Hocky, Gregory A. Voth, Laurent Blanchoin, Jean Louis Martiel, Enrique M. De La Cruz

Research output: Contribution to journalArticle

Abstract

Computational and structural studies have been indispensable in investigating the molecular origins of actin filament mechanical properties and modulation by the regulatory severing protein cofilin. All-atom molecular dynamics simulations of cofilactin filament structures determined by electron cryomicroscopy reveal how cofilin enhances the bending and twisting compliance of actin filaments. Continuum mechanics models suggest that buckled cofilactin filaments localize elastic energy at boundaries between bare and cofilin-decorated segments because of their nonuniform elasticity, thereby accelerating filament severing. Here, we develop mesoscopic length-scale (cofil)actin filament models and evaluate the effects of compressive and twisting loads on strain energy distribution at specific interprotein interfaces. The models reliably capture the filament bending and torsional rigidities and intersubunit torsional flexibility measured experimentally with purified protein components. Buckling is predicted to enhance cofilactin filament severing with minimal effects on cofilin occupancy, whereas filament twisting enhances cofilin dissociation without compromising filament integrity. Preferential severing at actin-cofilactin boundaries of buckled filaments is more prominent than predicted by continuum models because of the enhanced spatial resolution. The models developed here will be valuable for evaluating the effects of filament shape deformations on filament stability and interactions with regulatory proteins, and analysis of single filament manipulation assays.

Original languageEnglish (US)
Pages (from-to)2624-2633
Number of pages10
JournalBiophysical journal
Volume112
Issue number12
DOIs
StatePublished - Jun 20 2017

ASJC Scopus subject areas

  • Biophysics

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    Schramm, A. C., Hocky, G. M., Voth, G. A., Blanchoin, L., Martiel, J. L., & De La Cruz, E. M. (2017). Actin Filament Strain Promotes Severing and Cofilin Dissociation. Biophysical journal, 112(12), 2624-2633. https://doi.org/10.1016/j.bpj.2017.05.016