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, 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.
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The authors apologize to their colleagues whose work could not be cited owing to space limitations. They thank K. Toropova, R. Hernandez-Lopez, J. Huang and S. Reck-Peterson for helpful comments on the manuscript and B. Malkova for providing electron microscopy data for figure 5a. A.J.R. is grateful to J. Iwasa for training on AutoDesk Maya software. The work in the authors laboratory was supported by: a Sir Henry Wellcome Postdoctoral Fellowship (092436/Z/10/Z) to A.J.R.; a Grant-in-Aid for Scientific Research (B) 23370073 from the Japan Society for Promotion of Science (JSPS) and a Japan Science and Technology Agency PRESTO award to T.K.; a Grant-in-Aid for Scientific Research (B) 23370075 from the JSPS to K.S., and grants BB/E00928X/1 and BB/BB/K000705/1 from the BBSRC (UK) and RGP0009/2008-C from the Human Frontiers Science Program to S.A.B.
The authors declare no competing financial interests.
- G protein-related fold
A characteristic arrangement of secondary structure elements and loops (such as switch I and switch II) shared by G proteins, myosins and kinesins, which indicates that these proteins originated from a common ancestor.
The microtubule-based core of eukaryotic cilia and flagella. The terms cilia and flagella are often used interchangeably, as both describe cellular appendages with an axoneme at their core. In this Review, we use cilia for consistency.
Organelles that enwrap cytoplasmic material in a double-membrane-bound structure and subsequently fuse with lysosomes, leading to degradation of the confined material.
- Immunological synapse
The interface formed between an antigen-presenting cell and a lymphocyte, such as a B cell or a T cell.
- Astral microtubules
Microtubules radiating from the spindle poles that do not contact the kinetochore or overlap with other microtubules in the spindle midzone.
- Crystal soaking
A technique in which a crystallized macromolecule is bathed in a ligand-containing solution. The ligand has the opportunity to bind the macromolecule of interest owing to diffusion through solvent-filled channels in the crystal.
- E1 helicase
A hexameric AAA+ ATPase protein from papillomavirus that encircles and translocates along single-stranded DNA, thereby unwinding DNA duplexes with a 3′ to 5′ directionality.
Snake-like movement of a polymer along a path, originally introduced by De Gennes in the field of polymer theory.
- Highly inclined and laminated optical sheet microscopy
A technique for visualizing fluorescently labelled single molecules in cells. To minimize background signal (which can confound single-molecule detection) the specimen is illuminated with an angled sheet of light.
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Roberts, A., Kon, T., Knight, P. et al. Functions and mechanics of dynein motor proteins. Nat Rev Mol Cell Biol 14, 713–726 (2013). https://doi.org/10.1038/nrm3667
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