BIROn - Birkbeck Institutional Research Online

    Intraflagellar transport dynein is autoinhibited by trapping of its mechanical and track-binding elements

    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.

    [img]
    Preview
    Text
    18375.pdf - Author's Accepted Manuscript

    Download (2MB) | Preview

    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 Schools and Departments > School of Science > Biological Sciences
    Depositing User: Administrator
    Date Deposited: 17 Mar 2017 09:15
    Last Modified: 29 Jul 2019 19:31
    URI: http://eprints.bbk.ac.uk/id/eprint/18375

    Statistics

    Downloads
    Activity Overview
    107Downloads
    147Hits

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item