The architecture and nucleotide-dependent conformational changes of the dynein motor domain were recently resolved in several recent structural studies.Dynein displays conspicuous differences from kinesin and myosin, including the independent stepping behavior of the two motor domains in the homodimer, its much weaker directional bias, and the long separation between the polymer-binding domain and the catalytic body of the enzyme.The dynein linker domain plays an important role in the mechanics of movement but also regulates specific transitions in the ATPase cycle.Dynein may use several mechanisms to bias its movement towards the minus end, including conformational changes of its linker domain, Brownian search, and an asymmetric binding mechanism of its microtubule-binding domain.