Fig. 5.

Schematic illustrations of intramolecular contacts. The P-end is at the top. Two actin subunits are shown (in yellow and cyan) from the longitudinal contact in one strand of the F-actin (a) and from the cofilactin filament (b). In a and b, the left panel is the front view and the right panel is the side view with the front surface on the left-hand side. In c–h, each panel is a side view. a A schematic illustration of F-actin. Each actin molecule is in the F-form, where the ID and OD are aligned to be flat. The ID–ID and OD–ID interactions are represented by blue and red arrows, respectively. b A schematic illustration of the cofilactin filament. Cofilin is in orange. Actin and cofilin interact with each other through three interaction sites, the F-site (blue), Gi-site and Go-site (red). The Gi-site is subdivided into two parts, the Gi_l-site (brown) and Gi_s-site (yellow). Part of subdomain 2 (residues 41–49) is disordered and presented by dotted lines. The outer domain is tilted and the nucleotide-binding cleft is closed. The ID–ID interactions remain (blue arrow) while the OD–ID interactions diminish (Fig. 3a, b). c–h Schematic illustrations of a multi-step model for cofilin binding to the actin filament. c, d Step 1. Cofilin binds to F-actin through the F-site (blue). The system at this stage is in equilibrium between the bound (c) and unbound (d) states. The OD of the ADP-bound actin subunit occasionally fluctuates (represented by the curved arrow). e Step 2. Cofilin bound through the F-site eventually approaches the Gi_l-site (brown), which is captured through binding of the flexible and extended side chains. f Step 3. The structural transition in the P-subunits is induced, and full G-site binding occurs (yellow and red). g, h An alternative pathway in which cofilin directly binds to F-actin through the Gi_l-site without F-site binding