Fig. 6: The proposed mechanism for two-way communications between MTBD and ATPase domain during the mechanochemical cycle of dynein.

a The three conformational states of MTBD revealed in this study. In the MT-unbound state, MTBD undergoes conformational equilibrium between MTBD-Low (left, +β-registry) and MTBD-High (middle, semi-α-registry). MT binding induces conformational changes of MTBD with sliding of CC1 (α-registry). b Mechanochemical cycles of dynein. In the ATPase-driven pathway (green), the hydrolysis of ATP (3 to 4–1) and subsequent release of Pi (4–1 to 4–2) shift the equilibrium of MTBD toward semi-α state (4–2) to increase the MT-binding affinity. After MT binding, the stabilized α-registry transmits the conformational changes to ATPase domain, thereby facilitating the powerstroke movements of the linker (4–3 to 5). In the MT-binding-induced pathway (pink), the ATP-bound dynein searches for a new binding site in the low-affinity state. Upon MT binding, the stabilization of the α-registry transmits the conformational changes to the ATPase domain, which facilitates ATP hydrolysis, Pi release, and the powerstroke all at once.