Cytoplasmic dynein, a member of the AAA (ATPases Associated with diverse cellular Activities) family of proteins, drives the processive movement of numerous intracellular cargos towards the minus end of microtubules. Here, we summarize the structural and motile properties of dynein and highlight features that distinguish this motor from kinesin-1 and myosin V, two well-studied transport motors. Integrating information from recent crystal and cryoelectron microscopy structures, as well as high-resolution single-molecule studies, we also discuss models for how dynein biases its movement in one direction along a microtubule track, and present a movie that illustrates these principles. 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.
ASJC Scopus subject areas
- Molecular Biology