Toropova, K;
Mladenov, M;
Roberts, AJ;
(2017)
Intraflagellar transport dynein is autoinhibited by trapping of its mechanical and track-binding elements.
Nature Structural & Molecular Biology
, 24
pp. 461-468.
10.1038/nsmb.3391.
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Abstract
Cilia are multifunctional 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 multimotor assemblies with kinesin-II. Combining these data with insights from single-particle EM, 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.
| Type: | Article |
|---|---|
| Title: | Intraflagellar transport dynein is autoinhibited by trapping of its mechanical and track-binding elements |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/nsmb.3391 |
| Publisher version: | https://doi.org/10.1038/nsmb.3391 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Motor protein function, Motor protein structure |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10097018 |
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