Fig. 1: Engineering controllable actin-binding switch tools (CASTs) from actin-binding motifs.
From: Turn-on protein switches for controlling actin binding in cells
Peptide actin-binding motifs (ABMs) adopt conformations capable of recognizing and binding filamentous actin (F-actin) (top panel), where the bound complexes are energetically favored. To control ABM binding to F-actin, intramolecular binders can be engineered into ABMs’ termini (bottom panels), giving rise to Controllable Actin-binding Switch Tools (CASTs). The intramolecular association leads to energetically favorable unbound forms in the presence of F-actin. ABMs can be either (i) conformationally constrained (bottom left) or (ii) sterically occluded (bottom right) to disrupt native F-actin binding. The introduction of a stimulus (red star) that relieves the constraint or steric hindrance would then favor the bound F-actin form of the CAST, turning ‘on’ binding to F-actin in a user-defined manner.
