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Remodeling of actin filaments by ADF/cofilin proteins - PubMed

  • ️Sat Jan 01 2011

Remodeling of actin filaments by ADF/cofilin proteins

Vitold E Galkin et al. Proc Natl Acad Sci U S A. 2011.

Abstract

Cofilin/ADF proteins play key roles in the dynamics of actin, one of the most abundant and highly conserved eukaryotic proteins. We used cryoelectron microscopy to generate a 9-Å resolution three-dimensional reconstruction of cofilin-decorated actin filaments, the highest resolution achieved for a complex of F-actin with an actin-binding protein. We show that the cofilin-induced change in the filament twist is due to a unique conformation of the actin molecule unrelated to any previously observed state. The changes between the actin protomer in naked F-actin and in the actin-cofilin filament are greater than the conformational changes between G- and F-actin. Our results show the structural plasticity of actin, suggest that other actin-binding proteins may also induce large but different conformational changes, and show that F-actin cannot be described by a single molecular model.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.

(A) Pure actin filaments, imaged by cryo-EM, are thinner than (B) filaments decorated with cofilin-2. Scale bar, 500 Å. (C) Stereo view of the 3D reconstruction of F-actin decorated with cofilin-2 (transparent surface) is shown with the corresponding pseudoatomic model of the complex (ribbons). Cofilin molecules are in red.

Fig. 2.
Fig. 2.

Cofilin forms four contacts with two adjacent actin protomers. (A) Actin residues 143–147 (green) and 343–346 (magenta) interact with cofilin residues 112–119 (cyan). (B) The C-terminal residues 349–354 (red) form a bridge of density with a loop 41–46 (blue) and the N terminus (residues 1–5 in black) of cofilin. (C) A small loop 154–158 (green) in cofilin contacts residues 242 and 243 (black) of actin, while cofilin residues 94–98 (blue) interact with residues 21–28 (red) and 90–96 (cyan) within SD1 of actin. (D) Residues 19–21 (magenta) of cofilin also make a contact with residues 90–96 (cyan) of actin.

Fig. 3.
Fig. 3.

Cofilin alters the conformation of actin protomers and the helical twist of the actin filament. When a cofilin molecule (A) is placed on the surface of the unperturbed actin filament (B) the α1-helix (green) of cofilin clashes with the SD1 of actin (magenta arrow), while the α4-helix (blue) has a steric clash with SD2 of actin (red arrowheads). (C) Rotation of the outer domain of actin by approximately 30° (red arrow) resolves these clashes. (D) The inner domain of actin (SD3 and SD4) is shown in gray, while the outer domain is colored. Rotation of the outer domain from G-actin conformation (green ribbons) to F-actin conformation (blue ribbons) by approximately 20° (black arrow) flattens the actin molecule. (E) Upon cofilin binding, the outer domain of actin rotates from the F-actin conformation (blue ribbons) by approximately 30° (red arrow) toward the opposite helical strand (red ribbons). (F) When cofilin-deformed actin protomers (E) are arranged into a helical filament having the normal symmetry (F), the α4-helix of cofilin clashes with the lower portion of SD1 of actin (red arrowheads). (G) The clash shown in F can be resolved by rotation of protomer n + 2 by 10° around the helical axis (red arrow).

Fig. 4.
Fig. 4.

Cofilin alters F-actin longitudinal contacts. The residues involved in contacts between the two adjacent actin protomers (plum and tan ribbons) in regular actin (A) and cofilactin filaments (B) are shown as colored spheres. The interface between SD3 and SD4 (yellow and green spheres) is not altered by cofilin and includes interactions between Glu205, Asp241, Asp244, and Glu245 (yellow) with Asp286, Thr324, Arg290, and Pro322 (green), respectively. In regular actin (A) residues His40, Val45, Lys61, Arg62, and Ile64 (red) form bonds with Tyr169, Tyr143, Glu167, Asp288, and Tyr166 (blue), respectively. Rotation of the outer domain of actin upon cofilin binding (B) disrupts all of the above bonds and introduces a bridge of density between Val45 and the C terminus of actin (residues 370–375 in cyan).

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