The structure of the dynactin complex and its interaction with dynein

Making a molecular motor fit for purpose Dynactin is an essential cofactor of the microtubule motor, cytoplasmic dynein. Dynactin contains 23 subunits built around a short filament of an actin-related protein (Arp1). How dynactin is assembled, how it functions with dynein, and why it is built around an actin-like filament is unclear. Urnavicius et al. combined cryo–electron microscopy structural studies and a crystal structure to determine the three-dimensional architecture of dynactin and how it interacts with dynein. Science, this issue p. 1441 Cryo–electron microscopy structures reveal how the 23-subunit dynactin complex is assembled and binds to the motor protein cytoplasmic dynein-1. Dynactin is an essential cofactor for the microtubule motor cytoplasmic dynein-1. We report the structure of the 23-subunit dynactin complex by cryo-electron microscopy to 4.0 angstroms. Our reconstruction reveals how dynactin is built around a filament containing eight copies of the actin-related protein Arp1 and one of β-actin. The filament is capped at each end by distinct protein complexes, and its length is defined by elongated peptides that emerge from the α-helical shoulder domain. A further 8.2 angstrom structure of the complex between dynein, dynactin, and the motility-inducing cargo adaptor Bicaudal-D2 shows how the translational symmetry of the dynein tail matches that of the dynactin filament. The Bicaudal-D2 coiled coil runs between dynein and dynactin to stabilize the mutually dependent interactions between all three components.