Engineering Novel Actin-Based Molecular Motors from the Microtubule-Based Motor Dynein

Abstract

Linear biomolecular motors such as myosin, kinesin and dynein are protein machines responsible for directional movement in the cell. Despite the extensive analyses that have been performed on these machines, the design and construction of a novel biomolecular motor still poses a formidable challenge. Here we adopt a bottom-up approach in which the existing protein modules from different cytoskeletal systems are combined to create new biomolecular motors. We show that the hybrid motors—combinations of a motor core derived from the microtubule-based dynein motor and non-motor actin-binding proteins (ABPs)—robustly drive the sliding movement of an actin filament. The filament-binding affinity of the hybrid motors was nucleotide dependent, but the dependence was reversed when compared to that of the original dynein. Moreover, the direction of actin movement was able to be reversed simply by changing the relative position of the motor core and the actin binding module. Our synthetic strategy will open a way to understanding the design principle of biomolecular motors and thus to manufacturing controllable biomachines that work, for example, along artificial tracks at nanometer dimensions.