Inter-head Tension of Cytoplasmic Dynein Regulates the Coordination between Two Heads*

Studying the coordination between two heads of a motor protein is crucial to understand the walking mechanism of the motor protein on cytoskeletal tracks. Previous experiments found that inter-head tension of a cytoplasmic dynein was able to regulate the coordination between its two heads. However, the molecular origin is largely unknown. Here we utilized a structure-based coarse-grained model to investigate the structural changes of a cytoplasmic dynein monomer responding to opposite forces. We identified the molecular origin of the coupling between the AAA ring of a cytoplasmic dynein and its binding affinity to microtubules. Importantly, our simulation explained why this coupling is regulated by the direction of forces. Based on this work, we established an analytical expression of the detach rate of cytoplasmic dynein with respect to forces, which matches well with experimental findings. Our results provide a molecular basis to understand the walking pattern of cytoplasmic dynein.