Two opposite effects of cofilin on the thermal unfolding of F-actin: a differential scanning calorimetric study

Dedova, Irina; Nikolaeva, Olga; Mikhailova, V. V.; Remedios, Cris G. dos; Levitsky, Dmitrii I.

doi:10.1016/j.bpc.2004.01.009

Cited by 41 publications

(65 citation statements)

References 40 publications

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“…38 Because boundaries between cofilin-bound and unbound actin subunits occur with a higher frequency at low binding densities than at high binding densities, local changes (i.e. boundaries) in the mechanical properties will be more prominent at binding densities where cofilin binds noncontiguously.…”

Section: Discussionmentioning

confidence: 99%

Cofilin Increases the Bending Flexibility of Actin Filaments: Implications for Severing and Cell Mechanics

McCullough

Blanchoin

Martiel

et al. 2008

Journal of Molecular Biology

208

254

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We determined the flexural (bending) rigidities of actin and cofilactin filaments from a cosine correlation function analysis of their thermally driven, two-dimensional fluctuations in shape. The persistence length of actin filaments is 9.8 µm, corresponding to a flexural rigidity of 0.040 pN µm 2 . Cofilin binding lowers the persistence length ∼5-fold to a value of 2.2 µm and the filament flexural rigidity to 0.0091 pN µm 2 . That cofilin-decorated filaments are more flexible than native filaments despite an increased mass indicates that cofilin binding weakens and redistributes stabilizing subunit interactions of filaments. We favor a mechanism in which the increased flexibility of cofilin-decorated filaments results from the linked dissociation of filament-stabilizing ions and reorganization of actin subdomain 2 and as a consequence promotes severing due to a mechanical asymmetry. Knowledge of the effects of cofilin on actin filament bending mechanics, together with our previous analysis of torsional stiffness, provide a quantitative measure of the mechanical changes in actin filaments associated with cofilin binding, and suggest that the overall mechanical and forceproducing properties of cells can be modulated by cofilin activity.

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Section: Discussionmentioning

confidence: 99%

Cofilin Increases the Bending Flexibility of Actin Filaments: Implications for Severing and Cell Mechanics

McCullough

Blanchoin

Martiel

et al. 2008

Journal of Molecular Biology

208

254

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“…Cofilin destabilizes F-actin via a shift in the mean twist of actin filaments [McGough et al, 1997;Galkin et al, 2001] and cooperative changes in longitudinal and lateral interprotomer contacts [McGough and Chiu, 1999;Galkin et al, 2001;McGough et al, 2001;Bobkov et al, 2002;Galkin et al, 2003;Bobkov et al, 2004]. Cooperative effects of cofilin on F-actin are evident also from the presence of "tilted" filament structure in segments free of cofilin [Galkin et al, 2002], differential scanning calorimetry (DSC) measurements [Dedova et al, 2004;Bobkov et al, 2006], and phosphorescence decay (anisotropy) studies with Cys 374 -labeled actin [Prochniewicz et al, 2005].…”

Section: Introductionmentioning

confidence: 99%

Severing of F-actin by yeast cofilin is pH-independent

Pavlov

Mühlrád

Cooper

et al. 2006

Cell Motil. Cytoskeleton

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Cofilin plays an important role in actin turnover in cells by severing actin filaments and accelerating their depolymerization. The role of pH in the severing by cofilin was examined using fluorescence microscopy. To facilitate the imaging of actin filaments and to avoid the use of rhodamine phalloidin, which competes with cofilin, α-actin was labeled with tetramethylrhodamine cadaverine (TRC) at Gln 41 . The TRC-labeling inhibited actin treadmilling strongly, as measured by εATP release. Cofilin binding, detected via an increase in light scattering, and the subsequent conformational change in filament structure, as detected by TRC fluorescence decay, occurred 2-3 times faster at pH 6.8 than at pH 8.0. In contrast, actin filaments severing by cofilin was pH-independent. The pH-independent severing by cofilin was confirmed using actin labeled at Cys 374 with Oregon Green ® 488 maleimide. The depolymerization of actin by cofilin was faster at high pH.

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“…Estimates of the length over which cofilininduced conformational changes and cooperative binding interactions propagate along actin vary, ranging from N = 1-2 up to N > 100 subunits (3,5,(12)(13)(14)(15)(16)(17)(18)(19)(20). Equilibrium (3,6,12,21) and transient kinetic (12,14) binding data are well described by models invoking positive cooperativity between nearest neighbors (N = 1-2).…”

mentioning

confidence: 99%

“…Equilibrium (3,6,12,21) and transient kinetic (12,14) binding data are well described by models invoking positive cooperativity between nearest neighbors (N = 1-2). In contrast, differential scanning calorimetric (13) and spectroscopic lifetime (15) measurements estimate allosteric propagation of changes in structure, stability, and/or dynamics over N > 100 subunits. More recently, a singlemolecule TIRF study measured positive cooperative binding interactions that propagated exponentially with a decay length of N ~24 subunits (18), and atomic force microscopic imaging directly observed a change in the crossover distance of N ~14 bare actin subunits towards the pointed-end side of the boundary, but no propagation in the bare actin subunits towards the barbedend side of the boundary (8).…”

mentioning

confidence: 99%

The actin filament twist changes abruptly at boundaries between bare and cofilin-decorated segments

Huehn

Cao

Elam

et al. 2018

Journal of Biological Chemistry

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Cofilin/ADF proteins are actin-remodeling proteins, essential for actin disassembly in various cellular processes, including cell division, intracellular transport, and motility. Cofilins bind actin filaments cooperatively and sever them preferentially at boundaries between bare and cofilin-decorated (cofilactin) segments. The cooperative binding to actin has been proposed to originate from conformational changes that propagate allosterically from clusters of bound cofilin to bare actin segments. Estimates of the lengths over which these cooperative conformational changes propagate vary dramatically, ranging from 2 to >100 subunits. Here, we present a general, structure-based method for detecting from cryo-EM micrographs small variations in filament geometry (i.e. twist) with single subunit precision. How these variations correlate with regulatory protein occupancy reveals how far allosteric, conformational changes propagate along filaments. We used this method to determine the effects of cofilin on the actin filament twist. Our results indicate that cofilin-induced changes in filament twist propagate only 1-2 subunits from the boundary into the bare actin segment, independently of the boundary polarity (i.e. irrespective of whether or not the bare actin segment flanks the pointed or barbed end side of the boundary) and the pyrene fluorophore labeling of actin. These observations indicate that the filament twist changes abruptly at boundaries between bare and cofilin-decorated segments, thereby constraining mechanistic models of cooperative actin filament interactions and severing by cofilin. The methods presented here extend the capability of cryo-EM to analyze biologically relevant deviations from helical symmetry in actin as well as other classes of linear polymers.

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Two opposite effects of cofilin on the thermal unfolding of F-actin: a differential scanning calorimetric study

Cited by 41 publications

References 40 publications

Cofilin Increases the Bending Flexibility of Actin Filaments: Implications for Severing and Cell Mechanics

Cofilin Increases the Bending Flexibility of Actin Filaments: Implications for Severing and Cell Mechanics

Severing of F-actin by yeast cofilin is pH-independent

The actin filament twist changes abruptly at boundaries between bare and cofilin-decorated segments

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