Functions and mechanics of dynein motor proteins

Key Points Cell biological studies have identified roles for dynein motors in many in vivo processes. These include transporting diverse intracellular cargo along microtubules, organizing microtubules within the cell division machinery and powering the beating of cilia and flagella. Unlike myosin and kinesin, which share an ancestry with G proteins, dynein evolved from the AAA+ superfamily of ring-shaped ATPases. In outline, the mechanochemical cycle of dynein is similar to that of myosin, but the underlying mechanism of its movement is quite different. Recent structural studies point towards a model in which nucleotide-driven flexing motions in the dynein AAA+ ring are coupled to the remodelling of a mechanical element called the linker domain. The ATPase and microtubule-binding domains of dynein are spatially separated by a coiled-coil stalk, which is thought to mediate allosteric communication via small sliding movements between its constituent α-helices. Single-molecule studies are starting to reveal how the paired motor domains in cytoplasmic dynein dimers move along microtubules, but the extent to which the motor domains communicate with each other and how much force they produce are controversial. Fuelled by ATP hydrolysis, dyneins generate force and movement on microtubules in a wealth of biological processes. A model for the mechanochemical cycle of dynein is emerging, in which nucleotide-driven flexing motions within the AAA+ ring of dynein alter the affinity of its microtubule-binding 'stalk' and reshape its mechanical element to generate movement. Fuelled by ATP hydrolysis, dyneins generate force and movement on microtubules in a wealth of biological processes, including ciliary beating, cell division and intracellular transport. The large mass and complexity of dynein motors have made elucidating their mechanisms a sizable task. Yet, through a combination of approaches, including X-ray crystallography, cryo-electron microscopy, single-molecule assays and biochemical experiments, important progress has been made towards understanding how these giant motor proteins work. From these studies, a model for the mechanochemical cycle of dynein is emerging, in which nucleotide-driven flexing motions within the AAA+ ring of dynein alter the affinity of its microtubule-binding stalk and reshape its mechanical element to generate movement.