FIGURE 8:

Proposed model for DDB motility enhancement by p150 dynactin. (A) Dynein can reside in the inactive phi conformation in solution, but forming a DDB complex results in dynein switching to an open conformation (Zhang et al., 2017). In the open-inverted conformation, DDB is more likely to diffuse along microtubules, while in the open-parallel conformation DDB is more processive. Top, p150 interaction with the microtubule promotes a tilted dynactin geometry that stabilizes the open-parallel conformation of dynein and results in enhanced processivity. Bottom, blocking p150 causes dynactin to adopt a more flexible upright geometry that promotes the open-inverted conformation of dynein and results in DDB diffusing on the microtubule. Thus, complexing with BicD2 and dynactin activates dynein by inhibiting the phi conformation, and interaction of p150 further activates dynein by stabilizing the open-parallel conformation of the two dynein heads. (B) Implications for bidirectional cargo transport in cells: enhancement of DDB processivity by p150 promotes net minus-end cargo transport.