Toropova, K. and Mladenov, M. and Roberts, Anthony (2017) Intraflagellar transport dynein is autoinhibited by trapping of its mechanical and track-binding elements. Nature Structural & Molecular Biology 24 , pp. 461-468. ISSN 1545-9993.
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Abstract
Cilia are multi-functional organelles that are constructed using intraflagellar transport (IFT) of cargo to and from their tip. It is widely held that the retrograde IFT motor, dynein-2, must be controlled in order to reach the ciliary tip and then unleashed to power the return journey. However, the mechanism is unknown. Here, we systematically define the mechanochemistry of human dynein-2 motors as monomers, dimers, and multi-motor assemblies with kinesin-II. Combining these data with insights from single-particle electron microscopy, we discover that dynein-2 dimers are intrinsically autoinhibited. Inhibition is mediated by trapping dynein-2’s mechanical “linker” and “stalk” domains within a novel motor-motor interface. We find that linker-mediated inhibition enables efficient transport of dynein-2 by kinesin-II in vitro. These results suggest a conserved mechanism for autoregulation among dimeric dyneins, which is exploited as a switch for dynein-2’s recycling activity during IFT.
Metadata
| Item Type: | Article |
|---|---|
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Depositing User: | Administrator |
| Date Deposited: | 17 Mar 2017 09:15 |
| Last Modified: | 02 Aug 2023 17:32 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/18375 |
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