Abstract
Dyneins are ATP-fueled macromolecular machines that power all minus-end microtubule-based transport processes of molecular cargo within eukaryotic cells and play essential roles in a wide variety of cellular functions. These complex and fascinating motors have been the target of countless structural and biophysical studies. These investigations have elucidated the mechanism of ATP-driven force production and have helped unravel the conformational rearrangements associated with the dynein mechanochemical cycle. However, despite decades of research, it remains unknown how these molecular motions are harnessed to power massive cellular reorganization and what are the regulatory mechanisms that drive these processes. Recent advancements in electron tomography imaging have enabled researchers to visualize dynein motors in their transport environment with unprecedented detail and have led to exciting discoveries regarding dynein motor function and regulation. In this review, we will highlight how these recent structural studies have fundamentally propelled our understanding of the dynein motor and have revealed some unexpected, unifying mechanisms of regulation.