Microtubule

Biology

Motor protein

Biophysics

Dynein

Dynactin

Chemistry

Cell biology

Nature

Dynein and its cofactor dynactin form a highly processive microtubule motor in the presence of an activating adaptor, such as BICD2. Different adaptors link dynein and dynactin to distinct cargoes. Here we use electron microscopy and single-molecule studies to show that adaptors can recruit a second dynein to dynactin. Whereas BICD2 is biased towards recruiting a single dynein, the adaptors BICDR1 and HOOK3 predominantly recruit two dyneins. We find that the shift towards a double dynein complex increases both the force and speed of the microtubule motor. Our 3.5 Å resolution cryo-electron microscopy reconstruction of a dynein tail–dynactin–BICDR1 complex reveals how dynactin can act as a scaffold to coordinate two dyneins side-by-side. Our work provides a structural basis for understanding how diverse adaptors recruit different numbers of dyneins and regulate the motile properties of the dynein–dynactin transport machine. Cryo-electron microscopy and single-molecule studies reveal that the adaptors BICDR1 and HOOK3 recruit two dynein molecules to dynactin and thereby increase the force and speed of the dynein–dynactin microtubule motor. In eukaryotic cells, the cytoplasmic protein dynein-1 (dynein) is the main transporter of cargoes towards the minus ends of microtubules—tube-like components of the cytoskeleton that, together with motor proteins, move material within the cell. Dynein is converted into a highly processive motor protein through binding both to its cofactor dynactin and to a cargo adaptor, such as BICD2, BICDR1 or HOOK3. BICD2 preferentially binds to one molecule of dynein and one molecule of dynactin. Using cryo-electron microscopy Andrew Carter and team show that, in contrast, BICDR1 and HOOK3 bind to a complex of two dyneins, which are brought together by a dynactin scaffold. The authors' single-molecule studies highlight that this configuration increases both the force and speed of the motor complex.

Cryo-EM shows how dynactin recruits two dyneins for faster movement