A hypothetical model for an ADF-H domain decorated actin filament. (A) A model of an ADF-H domain–decorated actin filament obtained by docking the Twf-C–G-actin structure in the 23-Å electron density map of an ADF/cofilin-decorated actin filament (Galkin et al., 2003). (B) Binding of Twf-C (and ADF/cofilin) in this model results in a large structural change of actin subdomain 2, where the so-called D-loop (shown in red) moves ∼17 Å away from the actin hot spot cleft. (C) In the model, the structural rearrangement of actin subdomain 2 also affects the interaction between the two actin strands by weakening contacts involving the so-called actin “hydrophobic loop” (colored in orange). Together, these changes in inter- and cross-filament interactions could contribute to weakening of the actin filament and lead to filament depolymerization by Twf-C and ADF/cofilin.