Cryo-electron tomography reveals that dynactin recruits a team of dyneins for processive motility.

Abstract

A key player in the intracellular trafficking network is cytoplasmic dynein, a protein complex that transports molecular cargo along microtubules. Vertebrate dynein’s movement becomes strikingly enhanced upon interacting with dynactin and a cargo-adapter, such as BicaudalD2. However, the mechanisms responsible for increased transport are not well understood, largely due to limited structural information. We used cryo-electron tomography to visualize the three-dimensional structure of the microtubule-bound dynein-dynactin complex from Mus musculus, and show that the dynactin-cargo-adapter complex binds two dimeric dyneins. This configuration imposes spatial and conformational constraints on both dynein dimers, positioning the four motor domains in close proximity and oriented towards the microtubule minus-end. We propose that grouping multiple dyneins onto a single dynactin scaffold promotes collective force production, increased processivity, and favors unidirectional movement, suggesting mechanistic parallels to axonemal dynein. These findings provide structural insights into a previously unknown mechanism for dynein regulation.